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Abstract Background Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease which affects areas rich in apocrine glands. The main disease manifestations are inflammatory nodules (IN) and draining tunnels (dT). The course and progression of the disease are difficult to predict. There is currently lack of any broadly accepted biomarker which may inform on the activity of hidradenitis suppurativa (HS). Draining tunnel (dT) formation is the hallmark of HS in the affected skin. The existence of a biomarker which may predict dT formation before dTs appear in skin may become a tool for early biological treatment. Calprotectin, also known as S100 A8/A9 protein has been shown to be involved in various inflammatory conditions, including HS. Aim of this study was to evaluate circulating calprotectin as an index of dTs in the affected skin. Methods The study group consisted of 40 patients with confirmed HS and varying disease activity, assessed by number of dTs and International Hidradenitis Suppurativa Severity Score System (IHS 4 score) . Plasma samples were collected and stored at -80°C until analysis. Calprotectin was measured with GCAL® turbidimetric assay (Gentian AS, Norway). Results Fifteen patients had mild HS and 25 patients had moderate/severe HS. Positive association was found between circulating calprotectin and the absolute dT count (Pearson’s r2 = +0.750; p<0.0001) and the IHS4 (International HS 4 score) (Pearson’s r2 = +0.671; p<0.0001). Circulating calprotectin was significantly increased in patients with more than 2 dTs. Plasma calprotectin greater than 0.5 mg/L was associated with odds ratio 8.00 (1.87 to 34.22; p = 0.005) for 2 or more dTs. Conclusions Calprotectin is presented, for the first time, as a biomarker which indicates the formation of dTs in the skin. Its use as surrogate of early start of biologicals and response to treatment remains to be explored.