BACKGROUND: Inflammatory markers and leukocyte profiles have not been longitudinally evaluated as objective signs of hidradenitis suppurativa (HS) severity. We sought to assess C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), and leukocyte profiles as reliable indicators of HS severity. METHODS: Retrospective cohort study of 404 patients seen at the Einstein/Montefiore HS Center, Bronx, New York, between March 2019 and November 2020. Associations of disease severity (HS-Physician Global Assessment) with inflammatory markers and leukocyte profiles were assessed by odds ratios (OR) and 95% confidence intervals (95% CI) incorporating up to four visits per patient, adjusting for baseline gender, age, BMI, and smoking status. RESULTS: Patients with severe disease had elevated CRP (OR 1.87; 95% CI 1.49, 2.34), ESR (OR 1.04; 95% CI 1.03, 1.04), IL-6 (OR 1.08; 95% CI 1.00, 1.16), leukocytes (OR 1.22; 95% CI 1.14, 1.31), neutrophils (OR 1.31; 95% CI 1.20, 1.42), eosinophils (OR 14.40; 95% CI 2.97, 69.74), basophils (OR 2.53; 95% CI 1.09, 5.85), monocytes (OR 5.36; 95% CI 2.49, 11.53), and neutrophil-lymphocyte ratios (OR 1.63; 95% CI 1.35, 1.96) but decreased lymphocytes (OR 0.86; 95% CI 0.68, 1.10). CONCLUSIONS: This novel longitudinal study of inflammatory markers and leukocyte profiles offers critical laboratory measures to confirm clinically determined disease severity over time.