Individuals with low socioeconomic status (SES) are at greater risk of contracting and developing severe disease compared to people with higher SES. Age, sex, host genetics, smoking, and Cytomegalovirus (CMV) serostatus are known to have a major impact on human immune responses and thus susceptibility to infection. However, the impact of SES on immune variability is not well understood or explored. Here, we used data from the Milieu Intérieur project, a study of 1,000 healthy volunteers with extensive demographic and biological data, to examine the effect of SES on immune variability. We developed an Elo-rating system using socioeconomic features such as education, income, and household to objectively rank SES in the 1,000 donors. We observed sex specific SES associations, such as females with a low SES having significantly higher frequency of CMV seropositivity compared to high SES females, and males from a low SES having significantly higher frequency of active smoking compared to high SES males. Using random forest models, we identified specific immune genes which were significantly associated with SES in both baseline and immune challenge conditions. Interestingly, many of the SES associations were sex-stimuli specific, highlighting the complexity of these interactions. Our study provides a new way of computing SES in human populations that can help identify novel SES associations and reinforces biological evidence for SES-dependent susceptibility to infection. This should serve as a basis for further understanding the molecular mechanisms behind socioeconomic status effects on immune responses and ultimately disease.