Abstract Background There is evidence of an association of severe coroanavirus disease (COVID-19) outcomes with increased body mass index (BMI) and male sex. However, few studies have examined the interaction between sex and BMI on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral dynamics. Methods Participants conducted RT-PCR testing every 24–48 hours over a 15-day period. Sex and BMI were self-reported, and Ct values from E-gene were used to quantify viral load. Three distinct outcomes were examined using mixed-effects generalized linear models, linear models, and logistic models, respectively: all Ct values (model 1), nadir Ct value (model 2), and strongly detectable infection (at least 1 Ct value ≤28 during their infection) (model 3). An interaction term between BMI and sex was included, and inverse logit transformations were applied to quantify the differences by BMI and sex using marginal predictions. Results In total, 7988 participants enrolled in this study and 439 participants (model 1) and 309 (models 2 and 3) were eligible for these analyses. Among males, increasing BMI was associated with lower Ct values in a dose-response fashion. For participants with BMIs greater than 29 kg/m2, males had significantly lower Ct values and nadir Ct values than females. In total, 67.8% of males and 55.3% of females recorded a strongly detectable infection; increasing proportions of men had Ct values <28 with BMIs of 35 and 40 kg/m2. Conclusions We observed sex-based dimorphism in relation to BMI and COVID-19 viral load. Further investigation is needed to determine the cause, clinical impact, and transmission implications of this sex-differential effect of BMI on viral load.