The potential impacts of injecting oxytocin (OXY) to sows in the early postpartum period on the quality of mammary tight junctions, milk composition, and immune status of sows and piglets were studied. Postparturient sows received i.m. injections of either saline (control [CTL]; n = 10) or 75 IU of OXY (n = 10). Injections were given twice daily (0800 and 1630 h) starting on d 2 of lactation (i.e., between 12 and 20 h after birth of the last piglet), totaling 4 injections. Milk samples were obtained before the first injection (d 2 morning [AM]), before the second injection (d 2 afternoon [PM]), and on d 4 PM and d 5 PM. Blood samples were obtained from sows before milking on d 2 AM, d 2 PM, and d 5 PM. On d 5 of lactation, a blood sample was obtained from 3 piglets per litter. Circulating concentrations of prolactin, IGF-I, lactose, and IgA in sows did not differ between treatments at any time (P > 0.10), but OXY sows had less IgG than CTL sows (P < 0.01) on d 2 PM before the second OXY injection. There were differences in milk composition on d 2 PM, with OXY sows having more IGF-I (P < 0.01), solids (P < 0.05), protein (P < 0.01), energy (P < 0.05), and IgA (P < 0.01) and a greater Na:K ratio (P < 0.01) than CTL sows. These differences were not seen in the next 2 milk samples, except for protein and IgA that still tended (P < 0.10) to be greater in OXY vs. CTL sows on d 4 PM (for protein) and on d 5 PM (for IgA) after the last injection. Milk lactose content was lower in OXY vs. CTL sows on d 5 PM (P < 0.01). Values for immunoglobulin immunocrit, IgG, IgA, and IGF-I in piglet blood did not differ between treatments (P > 0.10). Injecting OXY to sows in the early postpartum period increased leakiness of the mammary tight junctions, improved composition of early milk, and may potentially affect immune status of neonatal piglets.