The impact of sex-specific body fat distribution on the susceptibility to five chronic infections, helicobacter pylori and human herpesviruses 3 to 6 (i.e. varicella-zoster, Epstein-Barr, cytomegalo- and human herpesvirus 6), has not previously been examined. In the present study, seropositivity was determined via multiplex serology in serum samples of study participants collected in 2006/08 and 2013/14 during the follow-up examinations F4 (n = 3080) and FF4 (n = 2279) of the German population-based baseline KORA S4 survey. We quantified the severity of overall and abdominal obesity by body mass index, body adiposity index, waist circumference, waist-to-hip ratio, and waist-to-height ratio. Using sex-specific logistic spline-models, cross-sectional and longitudinal associations between obesity measures and seropositivity of the previously mentioned infections were investigated. Overall and abdominal fat content were significantly associated with seropositivity of varicella-zoster virus in both cross-sectional and longitudinal analyses among women. In addition, a non-significant inverse relationship with Epstein-Barr virus seroprevalence in both sexes and a trend towards a positive association with human herpesvirus 6 seropositivity in women were observed. Therefore, in women total body fat may be associated with VZV-seropositivity and may influence the reactivation of the varicella-zoster virus, independent of adipose tissue distribution.