However, the compromised club received some positive injury news on Saturday. Malik Mustapha was activated from the physically unable to perform (PUP) list, per ESPN’s Adam Schefter. The promising second-year safety should make his season debut against the Tampa Bay Buccaneers in Week 6.

49ers anticipate Malik Mustapha return in Week 6

Mustapha had a strong rookie campaign for the 49ers. The former fourth-round draft pick recorded 72 total tackles (32 solo) with an interception and five passes defended in 16 games last season.

Mustapha worked his way into the 49ers’ starting lineup in Week 4 and remained a starter for the rest of the year. However, he re-aggravated an ACL injury in the season finale. While he avoided a tear, Mustapha required surgery to address the ailment.

San Francisco placed the 23-year-old defender on the PUP list in August, sidelining him for the first four games of the 2025 season. Then, after a Week 5 win over the Los Angeles Rams, the 49ers opened Mustapha’s practice window. The move gave the team 21 days to activate the sophomore defensive back. Now it appears Mustapha is ready to take the field.

The 49ers’ 15th-ranked defense could use a boost. The unit is rebuilding under Robert Saleh after losing several key players to free agency over the offseason. With Bosa out for the year San Francisco could pursue a trade to fill the void left on the edge. The 49ers are rumored to be interested in Cincinnati Bengals star Trey Hendrickson.

The team is also hurting on the offensive side of the ball. However, backup QB Mac Jones has filled in admirably. Despite missing their starting QB, top three receivers and All-Pro tight end at times this season, the 49ers boast the league’s top passing offense.

Ricky Pearsall will join Purdy on the sideline in Week 6. Wideout Jauan Jennings is questionable and George Kittle is likely out again for the 49ers’ clash with the Buccaneers on Sunday.