Increased plasma NEFA concentrations and compromised immune responses are associated with increased disease susceptibility during farrowing and lactation. Increased plasma NEFA concentrations cause changes in the fatty acid (FA) content of plasma lipid fractions and peripheral blood mononuclear cells (PBMC) that could modify inflammatory responses. The goals of this study were to describe changes in plasma lipid composition and to characterize the FA content and proinflammatory phenotype of PBMC in periparturient and lactating sows. Blood samples from 10 sows were collected at 2 wk prefarrow, at 2 d after farrowing (hereafter referred to as farrowing), and at 18 d of lactation (hereafter referred to as lactation). Total lipids and lipid fractions were extracted from plasma and PBMC. Isolated PBMC also were assessed for gene expression of proinflammatory cytokines and enzymes involved in lipid mediator biosynthesis using quantitative PCR. The FA profile of plasma NEFA, phospholipids, neutral lipids, and PBMC phospholipids differed from the composition of total lipids in plasma. At farrowing and lactation, the proportion of palmitic and stearic acids increased (P<0.05) in the plasma NEFA and phospholipid fractions in comparison with prefarrowing concentrations. At the same time, the concentration of palmitic and linoleic acids increased (P<0.05) in the PBMC phospholipid fraction. Omega-3 FA, including docosapentaenoic and docosahexaenoic, increased (P<0.05) at farrowing in plasma and PBMC phospholipids compared with prefarrowing and lactation. Gene expression of IL-1β, IL-6, IL-8, and tumor necrosis factor-α (TNFα) decreased (P<0.05) after farrowing and in lactation. Similarly, cyclooxygenase expression was reduced during lactation when compared with farrowing (P<0.05). This study demonstrated changes in FA composition of serum lipid fractions and PBMC cellular membranes. Furthermore, it provided an initial assessment of inflammatory responses in mononuclear cells as a function of plasma and PBMC content of saturated and omega-3 FA. Future studies need to address the effect of increased NEFA concentrations, the main hallmark of lipid mobilization, and changes in plasma and cellular lipid profiles on immune function.