Osaka lit the Olympic cauldron on Friday and was widely hailed as the 'face of the Games', with enormous expectation that she would go on to triumph for hosts Japan.
The early exit of world number one Ash Barty seemed to help her case, but Osaka lost 6-1 6-4 to her Czech opponent in an hour and eight minutes.
Pressure has grown on the IOC to confirm the Games, due to start on July 24, will not go ahead as scheduled because of the COVID-19 pandemic.
The virus has killed 14,457 people worldwide and that figure continues to rise.
IOC president Thomas Bach this week stated that different scenarios for staging the Games are being considered and on Sunday revealed a timeframe for a call to be made.
The IOC outlined that modifying existing operational plans for the Games to go ahead on July 24 and changing the start date are being considered.
It explained that "critical venues" may no longer be available and raised logistical concerns such as hotel bookings and the potential impact on the calendar of "at least 33" Olympic sports.
Full commitment, the IOC added, would be required from all parties when coming up with a plan of action.
Bach has written to the global athlete community to inform them of the organisation's approach.
He wrote: "Human lives take precedence over everything, including the staging of the Games.
"The IOC wants to be part of the solution. Therefore we have made it our leading principle to safeguard the health of everyone involved, and to contribute to containing the virus.
"I wish, and we all are working for this, that the hope so many athletes, NOCs and IFs from all five continents have expressed will be fulfilled: that at the end of this dark tunnel we are all going through together, not knowing how long it is, the Olympic flame will be a light at the end of this tunnel."
The 20-time grand slam champion was knocked out of the French Open at the semi-final stage by eventual winner Novak Djokovic.
And, with just a two-week gap to the grass-court slam in London, the 35-year-old has opted against taking part at the All England Club or the Games in Tokyo.
"Hi all, I have decided not to participate at this year's Championships at Wimbledon and the Olympic Games in Tokyo," the Spaniard tweeted.
"It's never an easy decision to take but after listening to my body and discuss it with my team I understand that it is the right decision.
"The goal is to prolong my career and continue to do what makes me happy, that is to compete at the highest level and keep fighting for those professional and personal goals at he maximum level of competition."
Nadal explained that the quick turnaround from a gruelling campaign in Paris to another tough schedule at Wimbledon presented too much of a risk to his fitness.
"The fact that there has only been two weeks between RG [Roland Garros] and Wimbledon didn't make it easier on my body to recuperate after the always demanding clay court season," he said.
"They have been two months of great effort and the decision I take is focused looking at the mid and long term.
"Sport prevention of any kind of excess in my body is a very important factor at this stage of my career in order to try to keep fighting for the highest level of competition and titles.
"I want to send a special message to my fans around the world, to those in the United Kingdom and Japan in particular.
"The Olympic Games always meant a lot and they were always a priority as a Sports person, I found the spirit that every sports person in the world wants to live. I personally had the chance to live 3 of them and had the honor to be the flag bearer for my country."
Nadal is a two-time Wimbledon champion and took gold at the 2008 Olympics in Beijing.
Osaka lit the Olympic cauldron on Friday and was widely hailed as the 'face of the Games', with enormous expectation that she would go on to triumph for hosts Japan.
The early exit of world number one Ash Barty seemed to help her case, but Osaka lost 6-1 6-4 to her Czech opponent in an hour and eight minutes.
Osaka played a dismal opening set but then looked to have raised her game a notch in the second, establishing an early break.
However, that did not herald a full-blown fightback as former French Open runner-up Vondrousova soon got back on level terms and forced Osaka to serve to stay in the contest.
From 15-40, Osaka saved two match points, but Vondrousova soon had a third opportunity and her spirited defence won out.
Osaka flung a backhand wide this time and Vondrousova had her prized scalp, securing a place in the quarter-finals at the expense of the world number two.
It was an untidy performance from Osaka who made 32 unforced errors to just 10 from Vondrousova.
This was Osaka's first tournament since pulling out of the French Open at the end of May, in the wake of a first-round win. She cited depression and anxiety issues in Paris after announcing she would not take part in news conferences during the tournament.
In 2019, Russia was handed a four-year ban from major international sporting events by the World Anti-Doping Agency (WADA).
WADA declared the Russian Anti-Doping Agency (RUSADA) non-compliant over inconsistencies in anti-doping data discovered during an investigation.
At the time, the International Olympic Committee (IOC) reiterated its support for Russia's ban, which meant athletes would be unable to compete under the Russian flag at the 2020 Olympics or the 2022 Winter Games.
In a landmark move on Thursday, the Court of Arbitration for Sport (CAS) confirmed Russia would be banned, albeit with the time frame cut from four years to two.
That will still discount Russia from participating in the Tokyo Olympics – pushed back to 2021 due to the coronavirus pandemic – plus the Winter Games in Beijing in 2022, and the next World Cup.
Russia will, however, be able to compete at the Euro 2020 football finals, which is also scheduled to take place next year, having been another event impacted by COVID-19.
This is because WADA's international standard for code compliance by signatories does not list UEFA as a "major event organisation".
Russian athletes wishing to compete at the Tokyo and Beijing Games will be able to do so, but only under a neutral banner.
CAS stated in its announcement: "This panel has imposed consequences to reflect the nature and seriousness of the non-compliance [to the WADC] and to ensure that the integrity of sport against the scourge of doping is maintained.
"The consequences which the panel has decided to impose are not as extensive as those sought by WADA. This should not, however, be read as any validation of the conduct of RUSADA or the Russian authorities."
CAS also said that its ruling aims to "effect cultural change and encourage the next generation of Russian athletes to participate in clean international sport".
In order to be reinstated at the end of the two-year ban, it was also ruled that RUSADA must pay a contribution of $1.27million to WADA, in respect of the costs incurred in investigating the authenticity of the data retrieved from the Moscow laboratory in January 2019.
RUSADA, under supervision from WADA or the Athletics Integrity Unit (AIU), was told it must conduct investigations into any cases impacted by the deletions or alterations of the Moscow laboratory data.
The Russian organisation must also provide any other support requested by WADA to assist in determining whether athletes whose samples are listed in the Moscow laboratory database have a case to answer.
The four-time gold medallist from Rio completed only one event in Tuesday's team competition at the Ariake Gymnastics Centre, registering the lowest score of the first rotation.
Biles left the floor with a trainer and, although she later returned donned in a tracksuit, she opted not to continue and remained to support her team-mates who could only secure silver behind the Russian Olympic Committee.
Following the team event, Biles opened up on her struggles at Tokyo 2020 and said she would take it day-by-day before making a decision.
USA Gymnastics subsequently announced she will not participate on Thursday and will continue to be evaluated before a decision is made on whether she takes part in the individual event finals, which take place next week.
"After further medical evaluation, Simone Biles has withdrawn from the final individual all-around competition at the Tokyo Olympic Games, in order to focus on her mental health," a USA Gymnastics statement read.
"Simone will continue to be evaluated daily to determine whether or not to participate in next week’s individual event finals. Jade Carey, who had the ninth highest score in qualifications, will participate in her place in the all-around."
USA Gymnastics hailed Biles for her decision to put her own well-being ahead of competing.
"We wholeheartedly support Simone's decision and applaud her bravery in prioritising her well-being," the governing body added.
"Her courage shows, yet again, why she is a role model for so many."