The forward will try to lead the Avalanche to a third consecutive victory over Detroit and help them avoid a sixth straight defeat away from home Tuesday night.
O'Reilly, Colorado's leading scorer in 2011-12, missed nearly half of this shortened season while locked in a contract dispute. That ended when the Avalanche matched Calgary's two-year, $10 million offer Thursday.
The center made his season debut at the start of a three-game trip Sunday but did not record a point in Colorado's 2-1 overtime defeat to Columbus.
"He was like everybody else," coach Joe Sacco said. "We didn't get a lot of offensive production from our lines. We didn't generate a lot because we weren't skating the way we normally skate."
Colorado has scored seven goals in its last four road games but has earned one point in each of the past three. O'Reilly, though, could be the key to the Avalanche (8-8-4) snapping their 0-2-3 skid away from home Tuesday.
He had three assists in the most recent game against Detroit, a 4-3 win at Joe Louis Arena on Feb. 25, 2012, and scored twice in a 4-2 home victory over the Red Wings on Dec. 4, 2011.
The Avalanche will need all the help they can get against a Detroit team that nearly ended NHL-leading Chicago's record point streak Sunday.
Tomas Tatar gave the Red Wings a lead early in the third period but they allowed a power-play goal with 2:02 remaining in regulation en route to a 2-1 shootout defeat.
"We were close but not close enough," captain Henrik Zetterberg said. "We just have to forget about it. We just have to come back here, work hard and win the next game."
Detroit (10-8-4) has gone 2-0-1 in its last three at home after a three-game losing streak there. The Red Wings have also outscored opponents 15-7 during a 3-1-1 overall stretch.
"There are a ton of positives," coach Mike Babcock said of Sunday's game. "I thought our defense was good again, and they're getting better and better. ... I thought we played hard as a group. In the end, we just didn't execute enough to get it done."
Along with another solid defensive effort, Babcock is hoping for Johan Franzen to continue his outstanding play against the Avalanche. The winger has 11 goals in his last 11 games versus Colorado, though he's gone six games without a point.
Avalanche captain Gabriel Landeskog has three goals and two assists in his last three contests against Detroit.
Colorado hasn't dropped six straight on the road since an 0-8-1 skid Oct. 26-Dec. 15, 2011.