Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with insulin resistance (IR), metabolic syndrome and increased cardiovascular risk. Adipokines are biologically active, pleotropic molecules which have been involved in the development of IR and in the pathogenesis of several chronic inflammatory conditions. The aim of the present study was to analyze serum concentrations of adiponectin, leptin, resistin and visfatin in patients with HS, and investigate their possible associations with IR, HS risk and disease severity. This case-control study enrolled 137 non-diabetic individuals (76 HS-patients and 61 age and sex-matched controls). Serum concentrations of adiponectin, leptin, resistin and visfatin, and the homeostasis model assessment of IR (HOMA-IR) were measured in all the participants. Serum adiponectin concentrations were found to be significantly lower, and leptin, resistin and visfatin levels were significantly higher in HS-patients than in controls. These differences remained significant even after adjusting for age, sex and body mass index, except for leptin. In a multivariate regression analysis, HOMA-IR was inversely correlated with adiponectin and positively associated with resistin levels. Furthermore, serum levels of resistin and visfatin were independently associated with HS risk. However, we found no association between serum levels of adipokines and HS severity. Our results suggest that reduced adiponectin and increased resistin serum levels may be surrogate biomarkers for IR in patients with HS. Moreover, resistin and visfatin might be independent risk factors for the development of HS.