Semyon Varlamov made 33 saves in his first start in two weeks for New York (37-28-9), which was coming off a 5-4 overtime loss at the Columbus Blue Jackets on Friday.
The Islanders are one point ahead of the Penguins, who have one game in hand, for the first wild card from the East.
"It's hard," New York defenseman Scott Mayfield said. "There's going to be games like that, and [we've] just got to regroup and get the next one."
Okposo gave the Sabres a 1-0 at 13:31 of the third. Ilya Lyubushkin's shot from the right point deflected off Islanders forward Anders Lee to the left circle, where Okposo scored off the near post.
"The work ethic [Okposo] puts in here, [we're] pretty excited every time he scores," Buffalo coach Don Granato said. "A great play by [Lyubushkin], who does a lot of grunt work. A lot of not limelight type work. So the two of them team up on that play, it was nice to see."