Background: Cytomegalovirus (CMV) is a deoxyribonucleic acid virus that affects a significant proportion of the worldwide population; after primary infection, it goes into a latent state and can be reactivated, primarily after a reduction in host immune defenses. Methods: This study evaluated the association of acute cytomegalovirus infection (CMV IgM) and Allostatic Load (AL) by sociodemographic factors using data from the National Health and Nutrition Examination Survey (NHANES) 2001–2004 among participants (aged 20–49 years). CMV infection was determined by the level of CMV IgM antibody in serum samples. AL was assessed as a combination of 10 biomarkers from the cardiovascular, inflammatory, and metabolic systems. The evaluation of the association between CMV infection and AL included descriptive statistics and logistic regression models, which were adjusted for demographic and behavioral covariates. Results: AL was more elevated among those who were older, male, those with lower education, those performing limited physical activity, and smokers. CMV was more elevated in females than males among those who consumed alcohol and cigarette smokers. In Pearson’s correlation analysis, there was a slight positive correlation between CMV IgM and AL, with triglycerides and Body Mass Index (BMI) the most strongly correlated with AL. Binary logistic regression showed no significant relationship between high AL and positive CMV IgM but did show a significant relationship between high AL and age (OR = 1.0592, 95% CI 1.0215–1.0983, p = 0.00715). The findings of this study provide insight into the relationship between CMV and AL and provide awareness of factors that affect their relationship. View Full-Text ►▼ Show Figures This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.