: Cutaneous leishmaniasis (CL) is a skin disease caused by parasites. Presepsin, irisin, and apelin are biomarkers that are involved in the inflammatory response. The aim of this study was to investigate the association between serum levels of specific biomarkers, such as presepsin, apelin, and irisin, and the clinical features, location, number, and size of lesions in patients with CL. : This study is a single-centre, prospective cohort study involving a total of 30 patients with skin lesions compatible with CL and 30 healthy matched controls. Age, sex, type of skin lesion, location of skin lesion, number of skin lesions, and diameter of skin lesions were recorded. The levels of presepsin, irisin, and apelin measured in the blood samples of the patient group were analysed in comparison to those in the healthy control group. : The findings revealed that presepsin levels were significantly elevated in the patient group compared to the controls ( = 0.000). However, no statistically significant differences were observed between the groups for irisin and apelin levels (-values 0.096 and 0.836, respectively). A negative correlation was identified between presepsin levels and the number of skin lesions, the diameter of the largest lesion, and the total diameter of the lesions ( = 0.000). : It appears that measuring presepsin levels in patients with CL may be beneficial. Presepsin has the potential to serve as a prognostic marker in CL, offering significant benefits in guiding clinicians in assessing disease progression and response to treatment.