Trailing by three goals to open the third period, the Senators rallied to tie the game 4-4, but fell short as David Perron scored the shootout winner to lead the Penguins to a 5-4 victory.
"The push back was great," said Ottawa's Bobby Ryan. "I liked the team's response. When you get down early it can go either way and I thought the guys came in after the first and regrouped and stuck together, but I certainly feel like we left one out there. That's the way I feel at least."
Sidney Crosby, with two goals, Kris Letang and Evgeni Malkin also scored for the Penguins (32-15-8) while Thomas Greiss made 29 saves.
Mika Zibanejad, Mike Hoffman Mark Stone and Kyle Turris scored for the Senators (21-22-10), playing their first of a five-game homestand. Robin Lehner, making his career-high seventh consecutive start, stopped 25 shots.
Down 3-0, the Senators started their comeback at 5:09 into the third when Zibanejad got Ottawa on the board after taking a nice pass from Ryan.
Ryan then picked up his second assist of the night as he and Hoffman worked the give-and-go, culminating with Hoffman's 18th of the season just minutes later.
Crosby regained the two-goal lead as he saw a loose puck in Lehner's legs and pushed it in.
"That's just a bad goal," admitted Lehner. "It catches the wrong side of my blocker and I couldn't find it and it was after the guys scored two quick ones like that. It happens, but the guys kind of got energy from it and went out and played our hearts out so all credit to them."
Ottawa went on to score goals 13 seconds apart to tie the game as Stone took a Turris pass from in close and then Turris scored through Greiss' pads to make it 4-4.
"We came in and said this team's going to be identified by how we respond and I thought for the most part throughout the year we've responded pretty well and I think (Thursday) was no different," said Ryan.
Playing their second game in as many nights, Crosby admitted the Penguins didn't play their best game, but said playing back-to-back wasn't the issue. If anything Pittsburgh seemed to sit back a little too early in the final 20 minutes.
"I don't think it started right in the third," said Crosby. "I thought the second we weren't great as well. I think we had one shot in the second period. We didn't really set ourselves up for a good third."
Despite numerous opportunities in the second period the Senators were unable to beat Greiss.
Ryan was awarded a penalty shot after being pulled down by Letang. Ryan had a great move, but Greiss read it well and made the stop.
Shortly after, Erik Karlsson fired a shot that bounced off Greiss' head and fell behind him, but the Penguins netminder somehow managed to keep it out of the net. Greiss then stopped Karlsson from in close.
The Penguins added to the Senators frustration as Malkin scored from the faceoff circle to make it 3-0.
The Penguins opened the scoring 61 seconds into the game as Letang beat Lehner on a wraparound.
Crosby picked up his 18th of the season after taking a great pass from Rob Scuderi and rifled a shot past Lehner to take a 2-0 lead midway through the period.
Notes- C Jean-Gabriel Pageau and D Patrick Wiercioch were healthy scratches for Ottawa. G Craig Anderson (hand) and D Chris Phillips (maintenance) are day-to-day for the Senators. C Zack Smith skated for the first time since injuring his wrist in December. D Christian Ehrhoff and RW Steve Downie were healthy scratches for Pittsburgh.Suggest a correction