Objectives The aim of this study was to explore the degree to which couples' relationship dissatisfaction and stressful life events during pregnancy predict the risk of infectious disease in the offspring during their first year of life. Methods Data were obtained from the Norwegian Mother and Child Cohort Study, conducted by the Norwegian Institute of Public Health. Pregnant women completed questionnaires in week 30 of pregnancy concerning the couples' relationship satisfaction and stressful life events. In follow-up questionnaires, the women reported whether their children (n = 74,801) had been subject to various categories of infectious disease: the common cold, throat infection, bronchitis, RS virus, pneumonia, pseudocroup, gastric flu, ear infection, conjunctivitis and urinary tract infection. Reports from two age groups of infants were used. Associations between the predictor and outcome variables were assessed via logistic regression and linear regression analyses. Results Separate logistic regression analyses for each disease and age group showed that prenatal relationship dissatisfaction and stressful life events were significantly associated with all reported categories of infectious disease. After controlling for socioeconomic factors, social support, smoking, breastfeeding, maternal depression, the sex of the offspring, and use of child care, 29 out of 32 tested associations were statistically significant. Finally, multivariate linear regression analyses showed that prenatal relationship dissatisfaction and stressful life events were significantly associated with the frequency, as well as the variety, of infectious disease in the offspring.