Acute coronary syndrome (ACS) comprises a pathophysiological spectrum of cardiovascular diseases related to atherosclerotic coronary plaque erosion. Oxidative stress and inflammation play pivotal roles in the development and progression of atherosclerosis, which affects circulatory proteins, including albumin and fibrinogen, thereby causing an imbalance in albumin to globulin and fibrinogen to albumin ratios. This study aimed to assess the effect of oxidative stress on circulatory proteins, correlate these parameters, and investigate their significance in patients with ACS. In this case-control study, the major blood proteins in patients with ACS and a control group were evaluated using standard methods. Out of 70 ACS cases, 75.7% had ST-elevation myocardial infarction (STEMI), 18.6% had non-STEMI, and 5.7% had unstable angina. The mean cardiac troponin I level in patients was 12.42 ng/mL. The patients demonstrated a significantly reduced level of human serum albumin (HSA), 3.81 ± 0.99 g/dL, compared to controls, 5.33 ± 0.66 g/dL. The albumin to globulin ratio (AGR) was significantly depressed in patients while their mean fibrinogen level and the fibrinogen to albumin ratio (FAR) were significantly higher. Multivariate logistic regression analysis showed that albumin and fibrinogen were significantly associated with the risk of ACS, showing the potential of these parameters to be used for risk assessment of ACS. The ischemia modified albumin (IMA) and protein carbonyls were significantly higher in patients which showed significant positive correlations with FAR. Albumin, IMA and protein carbonyls were found to have high diagnostic sensitivity and specificity for ACS. Overall, these circulatory and modified proteins in ACS patients, particularly lower HSA, AGR, and higher IMA and protein carbonyls may help assess risk.