Clinically significant cryptococcal disease is typically seen in patients with human immunodeficiency virus (HIV). However, Cryptococcosis has also been observed among non-HIV immunocompromised hosts. Cryptococcosis and tuberculosis (TB) infections both occur due to impaired cell mediated immunity but co-infection is rare among immunocompromised patients. Co-infection of these pathogens is even less reported in immunocompetent hosts. We present a case of Cryptococcal left native knee septic arthritis with tibial osteomyelitis in an HIV negative patient with recently active tuberculosis.