DeKeyser injured his back during a 5-2 loss to the Vancouver Canucks on Oct. 22 and has missed the past 26 games. He has four assists in eight games this season.
"Now, we've played without him for a long time," Blashill said. "He could be out potentially for the season and not having him is the reality of our situation. So we have face the reality head-on, which means that the other guys have to step up and play really good hockey. Is it challenging? Sure it's challenging. We were hoping to get him back."
Blashill said that DeKeyser was making progress before having a setback that led to surgery.
"When he's healthy, he's our top defenseman and I think he's one of the most underrated defenders in the League," Blashill said. "He obviously has a huge impact on our team."
The Red Wings placed defenseman Jonathan Ericsson on injured reserve Tuesday and recalled defenseman Brian Lashoff from Grand Rapids of the American Hockey League. Ericsson has no points in nine games this season.
Lashoff could become the 12th defenseman to play for the Red Wings this season when they host the Columbus Blue Jackets at Little Caesars Arena on Tuesday (7:30 p.m. ET; FS-D, FS-O, NHL.TV).