Biology and pathogenesis of chikungunya virus (CHIKV) are not clearly established. Host factors play an important role in determining the progression and severity of the disease. Polymorphisms in the promoter region of CD209 gene (rs735239, rs4804803, rs2287886) and OAS1 (rs1131454 and rs10774671), OAS2 (rs15895 and rs1732778), and OAS3 (rs2285932 and rs2072136) genes were investigated in 100 patients with CHIKV infection and 101 healthy controls to find out the association of these polymorphisms with CHIKV infection. To evaluate the association of OAS and CD209 gene polymorphisms with the presence or absence of disease symptoms in CHIKV-infected patients. DNA was extracted and typed using polymerase chain reaction followed by restriction fragment length polymorphism methods. Results revealed that the allele and genotype frequencies of OAS1, OAS3, and OAS2 gene polymorphisms were not different between healthy controls and CHIKV patients. The frequency of CD209 gene G/G genotype of rs4804803 was significantly higher in CHIKV patients compared to healthy controls (p = 0.046). The present study suggests that rs4804803 GG genotype of CD209 gene is associated with susceptibility to CHIKV infection. To conclude, the present preliminary study suggests that OAS gene cluster and CD209 gene polymorphisms influence the risk of developing clinical symptoms in CHIKV-infected patients. Further follow-up studies with a large number of samples are needed to assess the role of these genes in association with post-sequela symptoms observed in CHIKV patients. A detailed research is required in these directions to understand the biology behind CHIKV infection and disease severity.