The 49ers figure to be without a Pro Bowl-caliber every-down linebacker for half the season.
And for at least another week or so, they will not have two of their top-four wide receivers.
The 49ers have struggled to find reliable replacements at those positions.
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In addition, they do not appear to be close to solving their issues in the defensive backfield with their pass coverage in nickel situations.
Coach Kyle Shanahan and his coaching staff have to do some problem-solving after their first three games of the season.
The 49ers must consider whether they can find upgrades at key positions through demotions and promotions.
Here are three positions where the 49ers could look to make changes to their depth chart after back-to-back poor performances in losses to the Minnesota Vikings and Los Angeles Rams:
San Francisco 49ers
Linebacker
The 49ers appeared to signal their discontent with veteran linebacker De’Vondre Campbell when they began working Dee Winters, a second-year player, into the mix on Sunday against the Rams.
But Winters aggravated an ankle injury in the second quarter and did not return.
“We want to keep working to get the best guys out there and Dee has had a good camp and he showed that he deserves the chance to push him (Campbell)," Shanahan said.
The 49ers signed Campbell to a one-year, $5 million contract after veteran linebacker Eric Kendricks reneged on a verbal commitment at the beginning of free agency and went to the Dallas Cowboys.
San Francisco sought to add a veteran linebacker who could fill in for Dre Greenlaw, who is expected to make a midseason return after sustaining a torn Achilles in the Super Bowl.
Campbell has struggled in pass coverage as an every-down linebacker. He has allowed 14 receptions on 16 targets for 149 yards and one touchdown through three games. He also was called for a critical pass-interference penalty of 25 yards that placed the Rams in position for the game-winning field goal on Sunday.
The 49ers also could consider moving linebacker Curtis Robinson into a more prominent role with base linebacker Demetrius Flannigan-Fowles also struggling.
Wide receiver
Deebo Samuel is expected to miss at least another game due to a calf injury. And first-round draft pick Ricky Pearsall is also out for at least another game. He is on the reserve/non-football injury list after being shot through the chest during an armed robbery attempt on Aug. 31.
Jauan Jennings stepped up in a big way on Sunday, catching 11 passes for 175 yards and three touchdowns.
Brandon Aiyuk has just 11 catches for 119 yards in three games after missing all of the offseason program and training camp while embroiled in a contract dispute. He ended up signing a five-year, $134.1 million contract.
The 49ers turned to Ronnie Bell in Week 3 to be the No. 3 receiver, and he did not come through when needed.
Bell has one catch for 12 yards in three games. He had a critical late-game drop that prevented the 49ers from getting into field-goal range for a potential game-winning attempt.
The 49ers should have a better option at wide receiver with veteran Chris Conley. He is a major contributor on special teams and has 221 career catches for 2,926 yards and 15 touchdowns in 10 seasons.
Rookie Jacob Cowing has not quite earned his way into a prominent role, Shanahan said.
“He's still working to get out there,” Shanahan said. “He is trying to get more comfortable with the offense and just earn a role. (He) gets closer and closer each week, (but he has) still got a bit to go, though.”
Cornerback
The 49ers felt good about their nickel defense when the season opened. But veteran Isaac Yiadom, who enters in nickel situations, has been exploited in coverage.
Yiadom has surrendered 10 completions on 13 targets for 123 yards and a touchdown. He also was flagged for a 48-yard pass-interference penalty against the Rams’ Tutu Atwell.
If the 49ers believe it’s time to make a change, they likely would turn to second-round draft pick Renardo Green.
Green played five snaps against the Rams on Sunday, which shows he has done enough to earn some trust from the coaches.
However, Green was called for a holding penalty in the end zone on a third-and-1 play from the 6-yard line late in the third quarter.
The 49ers opened the season with the players they believed gave them the best chance to win games.
The question is whether they’ve seen enough through three games to warrant any changes to their lineup.