Background: Maternal dietary docosahexaenoic acid (DHA) intake is thought to affect development in the offspring. Objective: We assessed the impact of maternal dietary DHA on behavior, brain fatty acid (FA) profile, and sickness response of offspring in pigs, a pertinent model for human nutrition. Methods: Sows (n = 24) were fed a diet with DHA-rich fish oil (FO) (20 g/kg) or high–oleic acid sunflower oil (HOSF) (20 g/kg) from day 61 of gestation through lactation. At 4 wk of age, 4 piglets per litter were weaned and mixed with piglets from other litters. Behavior was observed in 4- to 8-wk-old piglets, and brain FA composition was analyzed at 4 (n = 15) and 14 (n = 12) wk. Thirteen-week-old piglets (n = 48) were subjected to a lipopolysaccharide (LPS) challenge. Body temperature, plasma cytokines, and motivation to approach a familiar human, indicative of a sickness response, were measured. Results: FO-fed pigs displayed more social activities (+262%, P = 0.02), played more (+61%, P = 0.03), and tended to show fewer oral manipulative behaviors directed at pen mates (-25%, P = 0.06) than did HOSF-fed pigs up to 4 wk after weaning. Brain DHA concentrations were higher in FO- than in HOSF-fed pigs up to 10 wk after supplementation (+50–10%, P <0.001), although differences declined with age. Body temperature (P <0.001) and tumor necrosis factor a and interferon ¿ concentrations (P <0.05) increased after LPS injection, but no diet effect was found (P > 0.10). LPS-treated pigs were less likely to approach the human than saline-treated pigs in the HOSF-fed (-29%, P = 0.0003), but not in the FO-fed group (-13%, P = 0.11). Conclusions: Maternal DHA beneficially affected offspring social behavior after weaning and mildly attenuated sickness behavior after an inflammatory challenge in pigs. These behavioral changes may be mediated by increased brain DHA proportions.