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Aims: In addition to systemic inflammatory response syndrome (SIRS), various clinical signs, microbiological findings and inflammatory markers could be associated with severe diabetic foot infections (DFI). Methods: This study included a retrospective cohort of 245 patients with DFI treated at San Juan de Dios Hospital in San José de Costa Rica. Erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP), CRP/albumin ratio, peripheral blood leucocyte ratios and the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) scoring system were evaluated. Univariate analysis was carried out between moderate and severe infections. ROC curves were plotted. Cut‐off value of inflammatory markers for diagnosing severe infections was established and then dichotomized to be included in a logistic regression model. A score was designed based on its results. Results: Skin necrosis (p < 0.01, OR = 8.5, 95% CI = 3.5–20.9), ESR > 94 mm/h (p < 0.01, OR = 2.5, 95% CI = 1.2–5.1), albumin < 2.8 g/dl (p = 0.04, OR = 2.0, 95% CI = 1.0–4.1) and neutrophil‐to‐lymphocyte ratio (NLR) > 4.52 (p < 0.01, OR = 3.3, 95% CI = 1.6–6.5) were found to be predictive of severe infections. Score >5 had a good diagnosis performance for classifying severe infections. Moderate infections with a score >5 had a worse prognosis than moderate ones. Conclusions: We found an association of necrosis, serum albumin, ESR and NLR values with severe DFI. The presence of these predictive factors of severity in cases of moderate infections was significantly associated with a higher rate of amputations and recurrences, longer duration of antibiotic treatment and longer hospital stays. DFI could be classified as mild, moderate, severe without SIRS and severe. [ABSTRACT FROM AUTHOR]