Cows that are less resilient to metabolic stress exhibit increased adipose tissue (AT) lipolysis and oxidative stress postpartum (PP). We hypothesized that increased AT lipolysis will be related to elevated subacute inflammation and higher release of endotoxins from AT to blood PP, and that seasonal heat stress may exacerbate these effects. The study included 24 multiparous dairy cows calving during winter (W, n = 12) or summer heat stress (S, n = 12) at the Volcani research farm (Israel). Cows were categorized retrospectively to those with low (LWL) or high weight loss (HWL) during the first month PP, indicating on metabolic resilience. Blood samples were obtained twice a week during the transition period for tumor necrotizing factor α (TNF-α), oxidative stress marker (malondialdehyde, MDA) and LPS-binding protein (LBP). Subcutaneous AT biopsies were collected at 7 d PP during S for immunoblots of LBP and TNF-α. Data were analyzed by PROC MIXED (SAS). Blood TNF-α was 6.7-fold higher in S vs. W (P < 0.0009), and was 1.8-fold higher in HWL than in LWL cows during S (P < 0.05), but not between HWL and LWL cows at W. Blood MDA was 5-fold higher in S than in W (P < 0.0001), and was 2-fold higher in HWL than in LWL (P < 0.05) during S, and tended to be higher in HWL vs. LWL at W (P < 0.1). Across seasons, blood LBP was 1.7-fold higher in HWL than in LWL at 7 d PP (P < 0.05). In AT of S cows, the abundances of LBP (P < 0.05) and TNF-α (P < 0.001) were higher in HWL than in LWL. Together, cows that were less resilient to metabolic stress had a higher inflammatory response and increased signs of endo-toxemia in blood and AT specifically during heat stress. Seasonal heat stress has a dramatic effect on the degree of oxidative stress, subacute inflammation and immune function in transition cows.