Objectives – To explore whether circulating endocan concentrations differ between adults with imaging-confirmed peripheral artery disease (PAD) and controls without clinically evident PAD, and to generate hypotheses regarding the relationship between endocan and PAD-associated endothelial and inflammatory activity. Methods – In this single-centre exploratory cross-sectional study, 56 patients with imaging-confirmed PAD were compared with 54 cardiovascular risk-enriched controls without clinically evident PAD based on pulse examination and handheld Doppler assessment. Serum endocan was measured by ELISA, and exploratory between-group and multivariable analyses were performed. Results – The distributions of major cardiovascular comorbidities were statistically comparable between groups; however, the comparator group itself had a substantial cardiovascular-risk burden, including coronary artery disease in 74.1%, diabetes mellitus in 46.3%, hypertension in 59.3%, hyperlipidemia in 83.3%, and smoking in 44.4%. Mean serum endocan concentrations were numerically higher in the PAD group than in the comparator group (218.8 ± 166.9 vs. 170.5 ± 90.0 pg/mL), but the between-group difference did not reach statistical significance (p = 0.063). PAD status was not independently associated with serum endocan following multivariable adjustment. Conclusions – In this exploratory cohort, serum endocan concentrations were numerically higher in patients with PAD, but the between-group difference was not statistically significant and no independent association with PAD was demonstrated after adjustment. Interpretation is materially limited by the cardiovascular risk-enriched comparator population, in whom generalized endothelial activation and possible subclinical PAD may have reduced between-group separation. These findings do not validate endocan as a PAD-specific diagnostic biomarker and cannot be extrapolated to comparisons with low-risk healthy populations. Rather, they generate hypotheses for future studies using uniformly phenotyped healthy and risk-matched comparator groups.