Rust, Hornqvist, and Schultz each missed Game 3. Hornqvist also missed Game 2. Each is out with an upper-body injury.
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"They're still day to day," coach Mike Sullivan said. "They skated this morning, but they are day to day."
Kuhnhackl has not played since Game 6 of the Eastern Conference Second Round against the Washington Capitals, and is day to day with a lower-body injury, Sullivan said.
The Penguins could opt to go with seven defensemen and 11 forwards, as they did in Game 3, which would be a game-time decision, Sullivan said. Defenseman Trevor Daley returned from a lower-body injury In Game 3, and defenseman Mark Streit dressed for the first time in the 2017 Stanley Cup Playoffs.
Rust and Hornqvist are significant losses for the Penguins, who have scored one goal in each of the first three games. Rust has five goals in 14 playoff games, Hornqvist has seven points (four goals, three assists) in 13 games, and Schultz has eight points (two goals, six assists) in 14 games.
"There's no excuses," Daley said. "[The Senators] have a lot of injuries too, I'm sure. A lot of guys are playing with injuries right now."
Murray entered Game 3 after Fleury allowed four goals on nine shots in the opening 12:52 of the Penguins' 5-1 loss. Sullivan named Murray as his starter Friday after declining to do so Thursday.