Forwards Perron, McDonald and T.J. Oshie missed a combined 129 games last season. While Perron remains sidelined with post-concussion symptoms dating to November, St. Louis (1-2-0) has also been without right wing Crombeen and defenseman Colaiacovo.
Crombeen is out indefinitely after suffering a broken left shoulder blade in St. Louis' preseason finale. Colaiacovo was placed on injured reserve Tuesday after suffering an upper-body injury during last Saturday's season-opening 4-2 defeat to Nashville.
McDonald's absence now puts the team in an even bigger hole.
McDonald, who missed 24 games with a concussion in 2010-11, returned to St. Louis on Friday for further examination after possibly suffering another one during Thursday's 3-2 loss at Dallas.
The 34-year-old veteran was bumped from behind by teammate Nikita Nikitin before getting hit in the head by the Stars' Vernon Fiddler. It's unknown if McDonald will rejoin the team on its current four-game trek.
In addition to the injury concerns, coach Davis Payne is also troubled by his team's efforts with the man advantage. The Blues went 0 for 5 and allowed a short-handed goal Thursday, and they have converted just 1 of 13 power-play opportunities this season.
"It's going to continue to be a work in progress," Payne said. "I thought it got better. Now we have to take that next step where the execution leads to a chance to be buried."
St. Louis hasn't been very efficient on the power play versus San Jose (1-1-0), converting just 11 of 104 opportunities during the Sharks' 20-3-3 run in this series.
After cruising to a 6-3 victory over Phoenix in last Saturday's season opener, coach Todd McLellan's team looked a bit rusty following a five-day layoff, losing 1-0 at Anaheim on Friday.
"We have some world-class players here that can score, so it was disappointing that we didn't score," said captain Joe Thornton, who has tallied four goals and 26 assists over his last 22 home games versus the Blues. "...We can't get shut out like that."
The Sharks outshot the Ducks 31-23 and had two great scoring opportunities in the game's final minutes. Joe Pavelski was also thwarted by Ducks goaltender Jonas Hiller on a quality scoring chance in the first period.
"When you get good looks like that, you've got to finish them," he said.
Thomas Greiss, who continues to impress while Antti Niemi and Antero Niittymaki are both out with injuries, made 22 saves. In his only appearance against the Blues, Greiss stopped 35 of 37 shots in a 4-2 road win Feb. 4, 2010.
Niemi has been recovering from having a cyst removed from his knee. He was, however, healthy enough to be Greiss' backup Friday and could make his season debut Saturday. Niemi went 2-1-0 with a 2.35 goals-against average in three meetings with St. Louis last season.
Jaroslav Halak, who has posted a 2.70 GAA while starting all three games for the Blues this season, is 0-2-0 with a 5.23 GAA over his last three games versus San Jose.
AccuScore has powered more than 10,000 simulations for every NHL game on ESPN.com, calculating how each team's performance changes in response to game conditions and opponent's abilities. Each game is simulated and the game is replayed a minimum of 10,000 times to generate forecasted winning percentages.