Physiologically, dairy cows experience inflammation during calving; however, an exacerbated inflammatory response in the early postpartum can negatively impair cow health and performance during lactation. It has been suggested that anti-inflammatory therapy may decrease inflammation after calving, reducing these negative effects. The objective of this study was to assess the effects of a new preventive strategy with acetylsalicylic acid (ASA) on BCS, BHB, and inflammation (haptoglobin; HP) in postpartum dairy cows. Dairy cows (n = 246) from one dairy farm located in central Pennsylvania were included in this study. Cows were blocked by parity and randomly assigned to 2 groups: 1) ASP (n = 121): within ~12 h after parturition cows received 2 treatments with ASA (200 mg/kg; 4 boluses) 24 h apart; or 2) UNT (n = 125): remained untreated. Blood samples were collected at 7 ± 3 and 14 ± 3 d in milk (DIM) to measure BHB and HP concentrations. BCS was visually assessed by one experienced veterinarian at 7 ± 3, 14 ± 3 and 50 ± 10 DIM. The data were analyzed using the MIXED and GLIMMIX procedures of SAS as a randomized block design. There was no difference in BCS at 7 ± 3, 14 ± 3 and 50 ± 10 DIM between groups. Although the proportion of cows with subclinical ketosis did not differ between groups at 14 ± 3 DIM (ASP = 10 ± 3.72%; UNT = 16 ± 4.96%), cows treated with ASA had lower serum BHB concentration at 14 ± 3 DIM (ASP = 0.99 ± 0.08 mmol/L; UNT = 1.18 ± 0.08 mmol/L) compared with UNT cows. There was no difference in HP concentrations at 7 ± 3 DIM between study groups. The results from this study suggest that treatment with ASA after calving may improve metabolic status during early lactation, which in turn may enhance welfare and health in dairy cows.