Humoral immune responses play a pivotal role in naturally acquired immunity to malaria. Several Plasmodium falciparum antigens have been described as targets of the host immunity. We assessed antibody responses against a panel of P. falciparum antigens in patients with uncomplicated falciparum malaria in two urban malaria-endemic of Côte d’Ivoire with different epidemiological strata. A cross-sectional analysis of blood samples gathered from participants older than 6 months, in Man and Bouake in Côte d’Ivoire with different transmission strata was performed. Standardized ELISA was used to measure total IgG levels against 5 specific-P. falciparum antigens (CSP, LSA3, SALSA, GLURP, AMA1). A total of 151 sera were analyzed. The combined data from the two sites showed a proportion of responders greater than 50% for all the antigens tested. Proportion of IgG responders was greater than 50% except for SALSA (36.73%) at Man site. At Bouake site proportion of IgG responder was less than 50% with CSP (37.50%) and LSA3 (25%). The lowest proportion was observed in lowest age group. Proportion of IgG responder increased with increasing age at the two sites. Variation in the proportion of responders across the two sites was similar. The levels of IgG against AMA1, LSA3, GLURP and SALSA increased with increasing age at Man site. In contrast only IgG level against AMA1 increased while IgG level against CSP decreased with increasing age at Bouake site. Overall, antibody levels against AMA1, CSP, GLURP and LSA3 were gender-independent. These findings may have significant implications in the design of future malaria vaccines trials