Background: Systemic inflammation in horses with heaves is poorly characterized. Objectives: To assess acute phase proteins (APP) and inflammatory cytokine profiles in serum of healthy horses and horses with heaves.Animals: Six healthy horses and 6 heaves-affected horses belonging to the University of Montreal. Methods: Prospective, observational study. Healthy and heaves-affected control horses were exposed to a 30-day natural challenge with hay and straw to induce clinical exacerbation of heaves. Serum samples were obtained by venipuncture before (T0) as well as after 7 (T7) and 30 days (T30) of stabling. Serum APP (haptoglobin, serum amyloid A protein [SAA] and C-reactive protein [CRP]) and cytokines (IL-2, IL-4, IFN-a, IL-10, IFN-c, and CCL-2) were measured using singleplex or multiplex ELISA.Results: Serum haptoglobin concentrations were significantly higher in heaves-affected horses at all time points with no overlap with those of healthy controls. They were also significantly increased by antigen challenge in both controls (T7) and horses with heaves (T7 and T30). Serum SAA was detected more frequently in heaves-affected horses compared with healthy controls at T7. There was no difference in serum concentrations of CRP, IL-10, IFN-c, and CCL-2 between groups, whereas IL-2, IL-4, and IFN-a remained undetectable in all samples.Conclusions and Clinical Importance: In heaves, haptoglobin is a marker of both acute and chronic systemic inflammation, whereas high concentrations of SAA indicate acute inflammation.