Hepatitis B is a viral infection that attacks the liver and can cause both acute and chronic disease. Most patients are asymptomatic when newly infected. However, some can develop acute hepatitis with symptoms that last several weeks, including yellowing of the skin and eyes, dark urine, extreme fatigue, nausea, vomiting and abdominal pain. There are several extrahepatic manifestations that are associated with chronic HBV infection, including arthralgia, weakness, nephritis, and generalized vasculitis. Leprosy is also an infectious disease caused by a bacillus, Mycobacterium leprae, which multiplies slowly. Leprosy mainly affects the skin, the peripheral nerves, mucosa of the upper respiratory tract, and the eyes. The co-infection of HBV and mycobacterium leprae can lead to various manifestations and complications. Hepatitis B co-infection worsen course of leprosy. Leprosy treatment can also lead to flare of latent HBV infection. In this case report, we discuss the challenges faced in diagnosing and treating co-infection and complication of leprosy in a patient with chronic hepatitis B infection. Keywords: leprosy; hepatitis B; leprosy reaction; vasculitis.