More than two billion people around the world are overweight or obese. Even in apparently healthy people, obesity has a potent effect on their quality of life. Experimental data indicate the role of infectious agents in systemic inflammation, revealing a correlation between the dietary habits of people with obesity and the level of systemic inflammation mediators, serum lipid concentration, and hormonal and immune status. This study aimed to determine the association of immune response and lipid metabolism gene polymorphisms with the risk of obesity. This study included 560 Caucasian participants living in Western Siberia (Russian Federation). A total of 52 polymorphic sites in 20 genes were analyzed using the 5' TaqMan nuclease assay. Four risk-associated polymorphic variants were discovered-two variants in immune response genes ( rs2229238, OR = 1.92, 95% CI = 1.36-2.7, = 0.0002 in the dominant model; rs1946518, OR = 1.45, 95% CI = 1.03-2.04, = 0.033 in the over-dominant model) and two variants in lipid metabolism genes ( rs10455872, OR = 1.86, 95% CI = 1.07-3.21, = 0.026 in the log-additive model; rs1137100, OR = 2.88, 95% CI = 1.52-5.46, = 0.001 in the recessive model). Thus, polymorphisms in immune response and lipid metabolism genes are potentially associated with the modification of obesity risk in the Caucasian population.