Objective: The aim of this study is to investigate the expression levels of Pentraxin 3, PTX3 in patients with septic cardiomyopathy, SCM and evaluate its diagnostic potential for predicting SCM. Methods: A prospective observational study was conducted involving 122 patients diagnosed with septic shock between February 2023 and August 2024. Demographic and clinical data, along with plasma PTX3 concentrations were recorded. Participants were categorized into two groups based on the presence of SCM. PTX3 concentrations and their dynamic changes were compared between the groups. The correlations between PTX3 concentrations and other clinical indicators were analyzed, and the influencing factors associated with SCM development were assessed. The predictive performance of PTX3 for SCM was evaluated using receiver operating characteristic, ROC curves. Results: SCM was identified in 24.6% of the participants. Plasma PTX3 concentrations at admission and on day 3 were significantly higher in the SCM group compared to the non-SCM group, p < 0.001. However, no significant differences were observed on day 7, p > 0.05. PTX3 concentrations decreased over time in both groups. Plasma PTX3 concentrations were correlated with procalcitonin, lactate, myoglobin, troponin I, the elevated levels of troponin I on day 2 compared to admission, Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Evaluation II score, and intensive care unit length of stay. Elevated plasma PTX3 concentrations were identified as an independent risk factor for SCM development. The area under the ROC curve for PTX3 in predicting SCM was 0.784, p < 0.001, with a cutoff value of 20.82 ng/mL, sensitivity of 0.767, and specificity of 0.707. Conclusion: Plasma PTX3 concentrations are markedly elevated in patients with SCM, indicating that PTX3 may serve as a reliable biomarker for the early diagnosis of SCM.