Sesham movie revolves around the character Meera (Geethu Mohandas) who is a young filmmaker, is making a film on the mentally-challenged living in an asylum. While filming them, Meera notices Lonappan (Yayaram) who seems very different from the others. She then follows him with her camera. She studies him, his activities and so on, and that seems to lead her to many revelations.
She even succeeds in getting Lonappan out of the asylum. She does this with the zest of a crusader, but the 'sane'(?) society around her seems to question her stand and actions. In such a society, Lonappan is a rather unwelcome person. What happens then forms the rest of the story.