Jaden Schwartz, Vince Dunn, Mike Hoffman, Sammy Blais and Zach Sanford are playing elsewhere, and new faces like Brandon Saad, Pavel Buchnevich, James Neal and Jake Neighbours are taking their place.
In fact, a new face is expected on all four of the team's forward lines for Saturday's season opener.
"I think we have a lot of guys that can play with anyone, and we're deep. We're going to have to be," said Blues forward Brayden Schenn. "We have a good division, it's a good League. We feel like we need depth all throughout the lineup, and we feel like we have it.
"If you look at our lineup, we have guys on every single line that can play against every other line on any team," Schenn added. "From looking at our forward lines, there's a little bit of everything on every line. Whether it's speed, playmaking, scoring ability or guys that are good at both ends of the ice. I think we're pretty well balanced."
In practice for the last week, Brandon Saad was skating with Ryan O'Reilly and David Perron on the top line, while Pavel Buchnevich was on the right wing with Schenn and Jordan Kyrou.
"Saad is a type of guy that's been around, and I know he's played a lot of hockey with (Jonathan) Toews in Chicago," Blues Head Coach Craig Berube said. "Toews is similar to O'Reilly, the way they play from the defensive side of things. In the offensive zone with Perron and O'Reilly, the way they like to hang onto pucks and play that o-zone style of hockey, I think he fits well in there protecting pucks, keeping it down low, working the boards and working the front of the net."
"I think with Schenn and Buchnevich, it's a little bit more of a rush line for me," Berube added. "There's more speed on that line. With a guy like Kyrou and the way he uses his speed, but also his shot, he can make plays. I feel like that line can be real dangerous off the rush."
There's plenty of depth in the third and fourth lines, too. Robert Thomas led the Blues in points in the preseason and has been centering newcomer James Neal and Vladimir Tarasenko, while 2020 first-round pick Jake Neighbours earned a roster spot in training camp and is expected to play with Tyler Bozak and Ivan Barbashev.
There is one caveat for Opening Night - Perron missed Friday's team practice in Vail, Colorado and will be a game-time decision for Saturday. If Perron doesn't play, Klim Kostin is a likely replacement.
Defensively, not much has changed. Familiar pairings are back with Marco Scandella and Colton Parayko, Torey Krug and Justin Faulk, and Jake Walman and Robert Bortuzzo.
Jordan Binnington is expected to start in goal.
