The Sharks entered their game in Ottawa on Friday with an NHL-best 25 points on the road, including four earned with two victories to start a five-game trip.
Unfortantely for San Jose, the Senators proved to be inhospitable hosts, scoring three third-period goals en route to a 4-2 victory at Canadian Tire Centre.
Bobby Ryan had a goal and an assist and Craig Anderson made 31 saves for Ottawa, which won its fourth in a row at home.
Joe Thornton and Brent Burns scored for the Sharks, and Alex Stalock made 31 saves.