The Inuit population of Nunavik (Canada) is exposed to immunotoxic organochlorines (OCs) mainly through the consumption of fish and marine mammal fat. We investigated the effect of perinatal exposure to polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) on the incidence of acute infections in Inuit infants. We reviewed the medical charts of a cohort of 199 Inuit infants during the first 12 months of life and evaluated the incidence rates of upper and lower respiratory tract infections (URTI and LRTIs, respectively), otitis media, and gastrointestinal (GI) infections. Maternal plasma during delivery and infant plasma at 7 months of age were sampled and assayed for PCBs and DDE. Compared to rates for infants in the first quartile of exposure to PCBs (least exposed), adjusted rate ratios for infants in higher quartiles ranged between 1.09 and 1.32 for URTIs, 0.99 and 1.39 for otitis, 1.52 and 1.89 for GI infections, and 1.16 and 1.68 for LRTIs during the first 6 months of follow-up. For all infections combined, the rate ratios ranged from 1.17 to 1.27. The effect size was similar for DDE exposure but was lower for the full 12-month follow-up. Globally, most rate ratios were > 1.0, but few were statistically significant (p < 0.05). No association was found when postnatal exposure was considered. These results show a possible association between prenatal exposure to OCs and acute infections early in life in this Inuit population.