Background: Systemic lupus Erythematosus (SLE) increases cardiovascular risk due to both traditional risk factors and disease-specific mechanisms like inflammation and autoimmunity. Pentraxin3 (PTX3) has emerged as a key biomarker, with elevated levels correlating with disease activity and subclinical cardiovascular dysfunction. PTX3 may assist identify people with increased cardiovascular risk and monitor the effectiveness of treatments aimed at reducing inflammation and preventing heart damage. Objective: This study aimed to investigate the relationship between disease activity, pentraxin levels, and Global Longitudinal Strain (GLS), hypothesizing that higher disease activity is associated with elevated pentraxin levels and a decrease in GLS. Patients and methods: This case-control study included 50 SLE patients and 50 age- and sex-matched healthy controls to compare these factors. Results: The study found significant differences between SLE patients and control subjects in terms of clinical symptoms, laboratory parameters, and elevated PTX3 levels, which correlated with disease activity. Cardiac parameters were mostly normal, though reduced GLS suggested potential myocardial dysfunction. PTX3 showed high sensitivity and specificity as a biomarker for differentiating SLE patients from healthy controls and was strongly correlated with SLE disease activity, supporting its potential role in monitoring the disease. Conclusion: In patients with SLE, a strong correlation between PTX3 levels and LV systolic function as measured by LV GLS, with the disease activity, potentially represents new tools to improve risk stratification in these patients. And reinforces its potential as an effective screening tool for early detection of subclinical LV dysfunction in patients with SLE, though further research is needed to fully establish its clinical utility.