We report a premature neonate born of Human Immunodeficiency Virus (HIV)-1 positive mother presenting with extensive osteomyelitis and massive periosteal reaction involving both femurs and left tibia. There was no collection of fluid in soft tissue or joints in ultrasonography and Doppler examination showed normal venous return in both the lower limbs. Blood culture revealed growth of Candida albicans sensitive to fluconazole. The mother did not take any antenatal care and her HIV status was evident only after delivery during routine screening. DNA PCR for HIV-1 of the neonate done on day 45 and day 48 were positive with a viral load of 12 million copies/mL and his CD4 count was 24%. He was diagnosed as severe HIV-associated clinical disease with severe immunosuppression as per WHO classification and was put on combination antiretroviral therapy, Pneumocystis chemoprophylaxis and fluconazole. He responded well to treatment, repeat x-ray done at 4 months was normal except mild bowing of both the femurs. In the present case we wanted to emphasize the need of proper antenatal care and universal HIV-testing as the key to prevent mother-to-child transmission and severe HIV disease as in this case.