Dyslipidemia has been documented worldwide among human immunodeficiency virus-infected (HIV) individuals and these changes are reminiscent of the metabolic syndrome (MetS). In South Africa, with the highest number of HIV infections worldwide, HIV-1 subtype C is prevalent, while HIV-1 subtype B (genetically different from C) prevails in Europe and the United States. We aimed to evaluate if HIV infection (subtype C) is associated with dyslipidemia, inflammation and the occurrence of the MetS in Africans. Three hundred newly diagnosed HIV-infected participants were compared to 300 age, gender, body mass index and locality matched uninfected controls. MetS was defined according to the Adult Treatment Panel III (ATP III) and International Diabetes Federation (IDF) criteria. The HIV-infected group showed lower high density lipoprotein cholesterol (1.23 vs. 1.70 mmol/L) and low density lipoprotein cholesterol (2.60 vs. 2.80 mmol/L) and higher triglycerides (1.29 vs. 1.15 mmol/L), C-reactive protein (3.31 vs. 2.13 mg/L) and interleukin 6 (4.70 vs. 3.72 pg/L) levels compared to the uninfected group. No difference in the prevalence of the MetS was seen between the two groups (ATP III, 15.2 vs. 11.5%; IDF, 21.1 vs. 22.6%). This study shows that HIV-1 subtype C is associated with dyslipidemia, but not with a higher incidence of MetS in never antiretroviral-treated HIV-infected Africans.