This study was undertaken to assess the biochemical changes induced in chronic schistosomiasis and/or chronic HCV, as well as to pinpoint the most significant parameters which could be used as dependable indices for the differentiation of single and coupled infections with or without liver cirrhosis. The selected patients were allocated into 2 broad groups: GrII (Schistosomiasis) which was subdivided into 3 subgroups: GrII(a) schistosomal patients with hepatosplenomegaly; GrII(b) hepatosplenic schistosomal patients with decompensated liver cirrhosis; GrII(c) schistosomal patients with no organomegaly. GrIII (Combined) comprised 2 subgroups: GrIII(a) schistosomal-HCV infection with decompensated liver cirrhosis; GrIII(b) schistosomal-HCV infection without liver cirrhosis. For statistical comparison normal healthy subjects were taken as a reference group (Gr I). Results showed that schistosomal patients without organomegaly manifested non significant changes in all studied parameters compared to normal controls. Highly significant elevations in serum ALT, AST, ALP and GGT activities were recorded in all other subgroups but the highest levels are reported in GrIIb. AST/ALT and direct/indirect bilirubin ratios were highest in GrIIIa (1.17 ± 0.26, 1.54 ± 0.37, respectively). Serum total protein and albumin levels showed the highest reduction (33 and 59%) concomitantly with the highest increase in γ-globulin level (75%) in GrIII(a). Blood total iron was significantly reduced in GrII(a,b) (15.6 and 12%) (8.8%) bilirubin, GGT and AST in this order are good discriminators between the different subgroups in GrII. On the other hand, ALT, AST, albumin, ALP, GGT, protein and direct bilirubin are the most significant indices to differentiate chronic schistosomiasis and the combined group with/or without liver cirrhosis.