The significance of Chlamydia pneumoniae infection in patients with multiple sclerosis (MS) is unclear. We determined the frequency of serum C. pneumoniae-specific immune complexes in patients with MS, neurological (OND) and healthy controls in a blinded, cross-sectional study. C. pneumoniae immune complexes were detected in 24% (38/156) of MS patients, 16% (11/69) of OND and 15% (77/499) of healthy controls. The odds ratio for all MS patients was 3.95 (95% CI: 2.15 to 7.24; P < 0.0001) accounting for the covariates: sex, age, socio-economic status and area of residence. The odds ratio for recently diagnosed MS patients was 4.33 (95% CI: 1.76 to 10.64; P = 0.001). Systemic C. pneumoniae infection is more frequent in MS patients than the healthy population and occurs early in the course of the disease.