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Background: Musculoskeletal health has also affected during COVID 19 pandemic at an unprecedented scale globally and characterized by marked deterioration of human health multidimensionally. It is conceivable that knee osteoarthritis (KOA) patients recovered from COVID-19 after second wave are at enhanced risk of Cardiovascular complications. Aim: The present study was intended to estimate the soluble vascular cell adhesion molecule (sVCAM-1), serum Paroxonase (PON) and markers of oxi-inflammatory stress in KOA patients diagnosed RT-PCR negative after second wave of COVID-19 and to determine their role in predicting Cardiovascular complications. Methodology: 80 KOA patients (35-50 years) of Delhi-NCR region were recruited and categorized into two groups (n=40 in each group; on the basis of their history of COVID infection). By using standard methods, study group parameters were estimated in KOA patients and statistically compared it with that of 40 healthy controls by using student’s t-test. Result: Serum sVCAM-1, MDA and IL-6 levels were significantly high (p<0.001) in Group II and Group III subjects as compared to healthy controls. Conversely, serum PON activity was found to be significantly low (P<0.001) in Group III as compared healthy controls. However, PON activity was altered insignificantly (p<0.1) with respect to Group II subjects. sVCAM-1 levels were positively correlated with MDA, IL-6 and Atherogenic index; and negatively correlated with PON activity (P<0.001) in post COVID KOA patients. Conclusion: Endothelial activation characterized by enhanced sVCAM-1 and reduced PON activity along with enhanced oxi-inflammatory stress status are more efficient molecular signatures of cardiovascular complications among Post COVID KOA patients. Therefore, Cardiovascular rehabilitation strategy along with reduction of oxi-inflammatory stress can be an effective approach in order to reduce the burden of CVD mortality among Post COVID KOA patients.