It was the first defeat in eight games for the Londoners, leaving them five points adrift of the top six.
Orient were punished for a sluggish start as Akpo Sodje and Niall Canavan steered Scunthorpe into a 2-0 lead in the opening 42 minutes.
Kevin Lisbie pulled a goal back on the stroke of half-time but after the interval Orient could not find a way past young keeper Eirik Holmen Johansen, on loan to the home side from Manchester City.
Slade said: "The mathematics are now simple. We have to win all our last five games if we are to make the play-offs.
"We have been on a really good run and to lose like this is difficult to take. We have created chances all afternoon but not taken enough of them. But we have left ourselves with a mountain to climb after starting so poorly."
- Sports & Recreation
- Akpo Sodje
- Kevin Lisbie