The distribution of Hepatitis GB-C/HG (GB-C/HG) and TT viruses (TTV) infections was investigated in selected populations from Gabon using Polymerase Chain Reaction (PCR) and Enzyme Linked Immunosorbent Assay (ELISA) for anti-Envelop 2 (anti-E2) GBV-C/HGV antibodies. Among pregnant women, 29 of 229 (12.6%) were Hepatitis GB virus-C and Hepatitis G virus (GBV-C/HGV) RNA positive (+) and 32 of 81 (39.5%) anti-E2 + versus 8 of 39 (20.5%) TTV DNA +. Among sickle cell anemia patients, 9.7% (3/31) were GBV-C/HGV RNA + versus 22.5% (7/31) TTV DNA +. For tuberculosis patients, the figures were 11.5% (4/35) and 0%. A study of hepatocellular carcinoma cases (n = 27) versus controls (n = 66) did not show significant differences for GBV-C/HGV RNA (10.7% versus 12.1%) and TTV DNA (44.4% versus 30.3%). According to phylogenetic analysis, the 15 GBV-C/HGV strains investigated clustered in group 1, the most common in sub-Saharan Africa whereas TTV sequences (n = 4) mostly clustered in genotypes G1 and one close to genotype G3. In the Gabonese populations investigated, GBV-C/HGV and TTV infections were highly endemic. These data are consistent with the low pathogenicity of these agents.