The Ducks recalled Despres on Monday from his long-term injury conditioning loan to their AHL affiliate in San Diego.
Despres hasn't played since Oct. 16, when he left the Ducks' fourth game of the season after a shoulder-to-head hit from Tyson Barrie. The Colorado defenseman was suspended three games for his actions.
Despres will be available to play Tuesday night, when the Ducks wrap up their East Coast road trip in Boston, coach Bruce Boudreau said.
"First of all, to have him back, when he's at his best he was very solid for us. He's a big, strong-bodied guy. He can play lots of minutes," Boudreau said Wednesday.
"What I'm expecting from him today is just a simple game, get his feet wet and do the right things and not try to overdo things on his first night. If we get that we'll be very happy."
Despres was injured one week after he agreed to a four-year, $18.5 million contract extension that underlined his remarkable rise with the Ducks.
Anaheim acquired the defenseman in a trade with Pittsburgh on March 2, and he cemented a permanent lineup spot in just 16 regular-season games. Despres added seven points and steady two-way postseason play during the Ducks' run to Game 7 of the Western Conference finals.
After a terrible start to this season, the Ducks are an impressive 9-3-1 since the Christmas break. Anaheim (21-18-7) is back in playoff contention, despite scoring the NHL's fewest goals by a wide margin.
Defenseman Cam Fowler has missed 12 games since Dec. 27 because of a sprained knee. The Ducks' ice-time leader returned to workouts with his teammates last week.
Josh Manson has seized the chance for playing time in Despres' absence. He has had two goals and two assists in 36 solid games for Anaheim.
ESPN's Joe McDonald and The Associated Press contributed to this report.