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Postpartum dysgalactia syndrome (PDS) is a condition affecting periparturient sows, characterized by a reduction in milk and colostrum synthesis shortly after farrowing. Insufficient milk production results in substantial economic losses due to increased piglet morbidity/mortality and premature sow culling. Since PDS develops within a few days following farrowing, the study objectives were to determine if periparturient immune cell profiles and circulating biomarkers differ in sows affected by PDS. We hypothesized differences in immune cells, circulating analytes, and inflammatory markers would exist at farrowing in sows that subsequently developed PDS compared to healthy herd-mates. Thirty-six sows with PDS symptoms were matched by parity and day of lactation with 36 healthy control (CON) sows. Diagnosis of PDS (timepoint 2) occurred on average 9.25 ± 2.67 d after farrowing. Blood samples and litter weights were collected at farrowing (timepoint 1) and at the onset of clinical PDS (timepoint 2). Piglets from PDS sows had lower average daily gain and higher mortality than piglets from CON (P< 0.01). Aspartate aminotransferase was increased (20%; P≤ 0.06) in PDS sows compared to CON at both timepoints. Additionally, blood urea nitrogen was increased in PDS sows at timepoint 1 and timepoint 2 (13%; P= 0.08 and 16%; P= 0.01, respectively). At timepoint 2, total protein, globulin, magnesium, and cholesterol were increased (P≤ 0.03) while γ-glutamyl transferase and albumin were decreased (P≤ 0.02) in PDS sows. Lipopolysaccharide-binding protein, an inflammatory biomarker, was increased (48%; P= 0.07) at timepoint 2 in PDS compared to CON sows. Collectively, these data indicate PDS sows have altered metabolism and appear immune activated compared to healthy herd-mates, and further investigation is needed to determine if PDS can be predicted at farrowing.Postpartum dysgalactia syndrome (PDS) is a multifactorial disorder characterized by reduced milk production and resulting in substantial economic losses to the swine industry due to negative effects on piglet growth and mortality. Evaluating hematological factors before and after PDS diagnosis could lead to timely and more targeted interventions to minimize piglet mortality and improve sow longevity.Postpartum dysgalactia syndrome (PDS) is a multifactorial disorder affecting periparturient sows characterized by a pronounced reduction (dysgalactia) in milk secretion. Insufficient milk production limits piglet growth, leading to increased piglet mortality and often removal of affected sows from the herd, ultimately compromising sow longevity and negatively impacting the profitability of swine operations. The objective of this study was to determine if differences in circulating immune cells, analytes, and inflammatory markers exist at farrowing in sows that subsequently develop PDS compared to healthy herd-mates. Thirty-six sows with PDS were matched by parity and day of lactation with 36 healthy control (CON) sows. Blood samples were collected at farrowing (timepoint 1) and at the onset of clinical PDS (timepoint 2). Differences in markers of tissue catabolism (blood urea nitrogen, β-hydroxybutyrate, aspartate aminotransferase, alanine aminotransferase) and inflammation (lipopolysaccharide-binding protein, haptoglobin, albumin) were observed in PDS sows compared to control, suggesting PDS sows have altered metabolism and are potentially immune activated compared to healthy herd-mates.