To evaluate HE4 as a potential biomarker for acute epididymitis.HE4 levels in serum were measured in 62 patients with acute epididymitis and 62 age-matched male controls.Both patients with epididymitis and the controls showed median HE4 values of 42 pmol/l (range: 10-560 pmol/l) and 34 pmol/l (range: 2-300 pmol/l), respectively (p = 0.3). Levels of HE4 did not change in the course of the treatment in patients with epididymitis. Regression analysis revealed no significant association between HE4 and any infection-linked variable. Multivariate analysis resulted in a number of factors associated with increased HE4 levels, which were renal dysfunction, cardiovascular diseases and malignancies.Although HE4 is not a biomarker for epididymitis and infection, it qualifies as a candidate for identifying patients with increased morbidity.