BACKGROUND Surgical procedures on obese patients are expected to have a high incidence of surgical site infection (SSI). The identification of pre-operative or early post-operative risk factors for SSI may help the surgeon to identify subjects in risk and adequately optimize their status. We conducted a study of the association of comorbidities and pre- and post-operative analytical variables with SSI following laparoscopic sleeve gastrectomy for the treatment of morbid obesity. METHODS We performed a prospective study of all morbidly obese patients undergoing laparoscopic sleeve gastrectomy as a bariatric procedure between 2007 and 2011. An association of clinical and analytical variables with SSI was investigated. RESULTS The study included 40 patients with a mean pre-operative body mass index (BMI) of 51.2±7.9 kg/m(2). Surgical site infections appeared in three patients (7.5%), of whom two had an intra-abdominal abscess located in the left hypochondrium and the third had a superficial incisional SSI. Pre-operatively, a BMI >45 kg/m(2) (OR 8.7; p=0.008), restrictive disorders identified by pulmonary function tests (OR 10.0; p=0.012), a serum total protein concentration <5.3 g/dL (OR 13; p=0.003), a plasma cortisol >30 mcg/dL (OR 13.0; p=0.003), and a mean corpuscular volume (MCV) <82 fL (OR 1.6; p=0.04) were associated with post-operative SSI. Post-operatively, a serum glucose >128 mg/dL (OR 4.7; p=0.012) and hemoglobin <11g/dL (OR 7.5; p=0.002) were associated with SSI. CONCLUSIONS The study supports the role of restrictive lung disorders and the values specified above for preoperative BMI, serum total protein and cortisol concentrations, and MCV, and of post-operative anemia and hyperglycemia as risk factors for SSI. In these situations, the surgeon must be aware of and seek to control these risk factors.