Malkin is day to day because of an upper-body injury, and also will not play against the Toronto Maple Leafs at Scotiabank Arena on Saturday.
The Penguins could have forwards Nick Bjugstad and Jared McCann in the lineup. They were acquired in a trade with the Florida Panthers for forwards Derick Brassard and Riley Sheahan, a second-round pick in the 2019 NHL Draft and two fourth-round picks in the 2019 draft.
The Penguins won 4-2 against the Tampa Bay Lightning on Wednesday but are 2-4-0 in six games since winning 10 of their previous 11 (10-1-0).
The Senators have lost two straight after winning four of their previous five (4-1-0). It's Ottawa's first game since its mandatory five-day break after the 2019 Honda NHL All-Star Weekend.
Ottawa won its first two games against Pittsburgh this season, outscoring the Penguins 8-5 in two wins at Canadian Tire Centre.