We studied blood lactate levels in 253 South African children on antiretroviral therapy. The prevalence of hyperlactatemia was 68% and severity was mild in most cases (69%). There was no association of symptoms and/or signs with hyperlactatemia. Independent predictors were lipo-dystrophy, time on antiretroviral therapy and baseline CD4 count. Increased awareness of hyperlactatemia in African children on antiretroviral therapy is warranted.