Objective: To investigate the association between TLR3 and TLR7 polymorphisms with susceptibility and clinical manifestations of Chikungunya Fever. Methods: A total of 177 individuals were studied: 73 patients with a confirmed diagnosis for Chikungunya virus and 104 non-infected individuals. Polymorphisms were determined by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Results: Our analysis showed an increased CC genotype frequency of the TLR7 rs3853839 polymorphism in male patients compared to control (29％ versus 2％, respectively; OR=20.69;95％ CI=2.55-167.36; P<0.001). Furthermore, arthritis (acute and chronic) was frequently found in CC male patients. On the contrary, 65％ of CG carriers were no-infected males (29％versus 65％, respectively; OR=0.23, 95％ CI=0.48-3.04; P=0.002). Finally, we observed a higher frequency of lymphopenia in CG male patients (CG=666.86±233.77, GG=1,314.27±752.29 cells/mm3, P=0.047). Conclusions: Our results suggest the TLR7 rs3853839 polymorphism is associated with lymphopenia and increased susceptibility to Chikungunya Fever in males.