PurposeTo determine whether the preoperative inflammatory serum C-reactive protein (CRP) and leukocyte count (LEUK) are associated with postoperative pain and complaints after otolaryngological surgery.MethodsRetrospective evaluation of 680 patients (33% female, median age 50 years) receiving otolaryngological surgery between November 2008 and March 2017 in a tertiary university hospital. Postoperative pain on the first postoperative day was assessed using the validated questionnaire of the German-wide project Quality Improvement in Postoperative Pain Treatment (QUIPS) including a numeric rating scale for assessment of postoperative pain (NRS, 0–10). The influence of preoperative parameters including CRP and LEUK on patients' postoperative pain was estimated.ResultsMean CRP value was 15.6 ± 34.6 mg/l and mean LEUK value 7.8 ± 3.2 Gpt/l. Patients with pharyngeal surgery had the highest CRP values (34.6 ± 52.9 mg/l), highest LEUK values (9.2 ± 4.2 Gpt/l) and the highest pain levels (3.1 ± 2.4 NRS) compared to all other surgical procedures (allp< 0.05). Higher postoperative pain was associated with LEUK values > 11.3 Gpt/l (r= 0.093,p= 0.016) and higher preoperative chronic pain (r= 0.127,p= 0.001). Multivariate analysis confirmed younger age, female gender, duration of surgery, preoperative chronic pain, type of surgery, and higher LEUK values > 11.3 as independent factors for postoperative pain. Perioperative antibiotics had no effect on the postoperative pain.ConclusionBeyond known factors, preoperative LEUK as inflammation marker is an independent predictor for pain on the first postoperative day.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00405-023-07980-4.