Strategies have been researched and implemented to reduce the number of people with diabetic foot ulcers (DFUs). One problem is the accurate assessment of DFU severity, which is the main factor in resource allocation and treatment choice. The primary objective of this study was to assess pentraxin-3 as a biomarker of an infected DFU (IDFU), the limb amputation level prognosis, and patient survival. The secondary objectives were to evaluate and compare other markers, including white blood cells (WBCs), C-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), and procalcitonin (PCT), for identifying IDFUs. Over a period of two years, 145 patients were followed; 131 of these were analyzed for this study. Pentraxin-3 was found to be a good predictor of death (p = 0.047). A comparison between IDFUs and DFUs revealed the following differences: PCT had the highest AUROC of 0.91, sensitivity of 93.7, and specificity of 83.3%. CRP had a cutoff value of 226 mg/L, an AUROC of 0.89, a sensitivity of 95.5%, and a specificity of 83.3%. Fibrinogen had an AUROC of 0.87 at a cutoff value of 5.29 g/L, with a good sensitivity and specificity of 85% and 87%, respectively. ESR had a cutoff value of 46 mm/h, an AUROC of 85%, a sensitivity of 83.7%, and a specificity of 83.3%. Pentraxin-3 showed promising results in predicting IDFUs and DFUs, and it served as a marker for the risk of death in IDFU patients during the 6 month follow-up. Other markers, including CRP, PCT, ESR, and fibrinogen, were more effective in differentiating between IDFUs and DFUs.