The star blue-liner has been out of the lineup since suffering a serious injury to his Achilles tendon on Feb. 13.
Karlsson was expected to miss the rest of the season following surgery to repair the tendon, which was sliced by a skate during a game. However, the defending Norris Trophy winner recently returned to practice and was back with regular defence partner Marc Methot for Wednesday's skate.
"I think he's closer," MacLean said when asked if Karlsson would play Thursday against the Capitals. "But I don't know if — there's always a chance, yes. But at this point he practised in a regular turn today so that's another step in the process and we'll see where it goes tomorrow."
Karlsson led NHL defenceman in goals (19) and points (78) last season and had 10 points in 14 games this season before the injury.
Entering Wednesday's games, the Senators were tied with the New York Rangers for seventh place in the Eastern Conference standings. Both teams have 52 points, one more than the Winnipeg Jets.
The top eight teams will reach the post-season. Ottawa hosts Philadelphia on Saturday and closes out the season the next day in Boston.
MacLean said Karlsson had "another good day."
"His conditioning level continues to get better, up to game speed," MacLean told reporters after practice. "I thought he practised well today."