Sunday started for the San Francisco 49ers with a familiar sight. Brock Purdy found Christian McCaffrey for a touchdown on a shovel pass, and the 49ers took a 7-0 lead over the Cleveland Browns on their opening possession.

From there it was a grind, as the Browns stifled Purdy and stunned the 49ers 19-17 with practice squad quarterback P.J. Walker playing for injured Deshaun Watson. Watson missed a second straight game due to a rotator cuff injury.

San Francisco had a chance to win the game late, but Jake Moody missed the would-be go-ahead 41-yard field goal with six seconds remaining.

The loss was the first for the 49ers, who drop to 5-1. They leave Cleveland with injury concerns that they largely evaded through the first five weeks of the season, as McCaffrey and wide receiver Deebo Samuel both left the game and did not return.

Wild final minutes include questionable call, missed FG

The 49ers led 17-16 late in the fourth quarter with a chance to grind out the final minutes of the clock. But they punted with 3:05 remaining after a three-and-out to set up Cleveland's game-winning field goal that was aided by a questionable unnecessary roughness call that kept the Browns' drive alive.

Officials flagged Tashaun Gipson Sr. for a hit on Elijah Moore that resulted in a first down for Cleveland on a third-down incompletion.

Officials flagged Gipson for contact with a defenseless receiver on the play. Replay showed that Gipson made contact with his shoulder to Moore's body and not his head. Instead of fourth-and-10 at their own 26-yard line, the Browns faced first-and-10 at their 41 with the penalty.

Eight plays later, Dustin Hopkins kicked a 29-yard field goal to give the Browns a 19-17 lead with 1:40 remaining. The 49ers had time to respond and appeared to be in line to win the game after driving 52 yards in 1:34 on their ensuing possession. Instead of going for more yardage on second-and-7 at the Cleveland 23-yard line, the 49ers opted for Purdy to spike the ball and set up Moody for the would-be game-winning field goal.

Moody's kicked sailed just outside the right upright, and the Browns held on for victory. While the late flag on Gipson is cause for frustration for the 49ers, they were in position to lose because of their stagnant offense.

Purdy struggles in first loss as 49ers' starter

After opening the game with a touchdown, the 49ers went nine straight drives before finding the end zone again. That touchdown was set up by the defense when Deommodore Lenoir intercepted Walker and returned the ball to Cleveland's 8-yard line.

San Francisco managed just 215 yards of offense on the day after entering Sunday averaging 402.6 yards per game, good for third in the NFL. Purdy, who thrust himself into the MVP conversation amid San Francisco's 5-0 start, had the worst day of his young career while suffering his first loss as the starting quarterback for the 49ers.

Purdy found himself under constant pressure from an aggressive Browns front anchored by All-Pro defensive end Myles Garrett. The result was a 12-of-27 effort for 125 yards with a touchdown and his first interception of the season. He was sacked three times.

49ers lose top weapons on offense

Making matters worse in San Francisco are the injuries to All-Pros McCaffrey and Samuel. McCaffrey sustained an oblique injury and tried to play through it. But he jogged to the locker room in the second half and didn't return. Jordan Mason led the 49ers' backfield in his absence, tallying 27 yards and a touchdown on five carries.

Samuel, meanwhile, left due to a shoulder injury in the first half and didn't return. It wasn't clear how or when he sustained the injury. The status of McCaffrey and Samuel moving forward wasn't immediately clear after the game.

Brandon Aiyuk led San Francisco's offense amid the injuries, tallying four catches for 76 yards. All-Pro tight end George Kittle struggled alongside Purdy while posting one catch for a single yard.

Walker likewise struggled while leading the Cleveland offense, finishing the game completing 18 of 34 passes for 192 yards with no touchdowns and two interceptions. But Cleveland's defense overcame the offensive woes to secure the Browns' win.