Post-partum relapses are a frequent phenomenon in multiple sclerosis (MS). The purpose of this study was to evaluate the timing and extent of new or growing T2-lesions after delivery in a cohort of Finnish MS patients. In addition to serial magnetic resonance imaging (MRI), the patients were followed up clinically with determination of relapse rate and expanded disability status scale. The annualized relapse rate was decreased during the last trimester of pregnancy [mean 0.14, standard deviation (SD) 0.14] when compared with the time before pregnancy (mean 0.64, SD 0.14; P = 0.04) and to time post-partum (mean 1.50, SD 0.45; P = 0.0002). New or enlarging lesions were detected in the post-partum images in 14 of 28 patients. Gadolinium-enhancing lesions in post-partum MRI were present in eight of 13 patients. There was a significant increase in the number of T2-lesions (P = 0.0009), in the total volume of MS-lesions measured from fluid-attenuated inversion recovery images (P = 0.0126) and in the number of diffusion weighted imaging hyperintense lesions (P = 0.0098) in the post-partum images. The clinical results support the earlier findings of decreased disease activity in late pregnancy. The clinical and MRI findings indicate that post-partum activation is an early and common phenomenon amongst mothers with MS.