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Abstract Introduction Toxoplasma gondii infection is considered as one of the most important opportunistic infections and cause of death in HIV patients. Methods In this cross‐sectional study, 334 HIV positive patients were included. The molecular test was performed by the restriction fragment length polymorphism–polymerase chain reaction method. Allelic frequency, haplotype analyses, and linkage disequilibrium were calculated. The odds ratio was calculated. The linear regression model was used to analysis of interleukin (IL)‐17A, IL‐17F, and IL‐6 single‐nucleotide polymorphism genotypes in HIV patients with and without toxoplasmosis. Results In total, 95 tested'patients (28.4%) were positive for toxoplasmosis. The risk of toxoplasma infection in the current study did not correlate with IL‐17 and IL‐6 polymorphism and the risk of contracting toxoplasma was also not significantly correlated in this study. There was no association between the frequency of alleles and the risk of toxoplasma infection in IL‐17 haplotype analysis. Conclusion The findings of this study revealed that there were significant differences in the serum levels of IL‐6 and IL‐17A, but not IL‐17F, between the case and control groups in various genetic models. However, these polymorphisms did not show a significant relationship with toxoplasma infection in HIV‐positive patients. This study represents the first investigation in Iran to explore the role of IL‐6 and IL‐17 polymorphisms in toxoplasma infection among HIV‐positive patients.