While one of the accused was arrested from Cuttack, the other was caught from Balasore, police said.
Police suspected involvement of at least six persons in the crime and are conducting raids at different locations to nab them.
Police said Sumit Behera was killed when he prevented the inmates from fleeing the de-addiction centre, "Prayas".
Behera, who had been working there as caretaker for the past three years, was tied up and strangulated to death by a group of inmates who had hatched a plan to escape.