The San Francisco 49ers lost two of their top playmakers to injury and ultimately suffered their first loss of the season, falling 19-17 to the Cleveland Browns on Sunday.
Star wide receiver Deebo Samuel was the first to exit, injuring his shoulder in the first quarter.
Later in the third quarter, Pro Bowl running back Christian McCaffrey sustained an oblique injury. He was officially announced as questionable to return, and was able to get back on the field, but after one carry, exited for good.
Before being ruled out, McCaffrey had 43 rushing yards on 11 carries and three receptions for nine yards with a touchdown.
McCaffrey, who was named to his second Pro Bowl last season, entered Week 6 leading the NFL with 510 rushing yards along with eight total touchdowns. With a TD reception against the Browns, he extending his consecutive game streak with a touchdown to 15 games - including the playoffs.
Samuel, who had just two rushes for 11 yards before getting hurt, came in with 20 catches for 302 yards and one TD. He also had 84 yards rushing on 16 attempts.
Facing the NFL's top defence, Brock Purdy and the depleted 49ers struggled to move the ball for much of the day.
San Francisco still had a chance to win, though, as Purdy marched the 49ers on a 52-yard drive to set up a potential game-winning field goal, but Jake Moody missed a 41-yard attempt in the final seconds.
It marked the first loss in a regular-season game for Purdy, who had won his first 10 such starts.
Purdy finished 12 of 27 for 125 yards with a touchdown and interception. He was also sacked three times.
The 49ers managed a season-low 215 yards of offence after racking up 421 total yards in last week's 42-10 win over the Dallas Cowboys.