Traditional Coronary Artery Bypass Graft (CABG) is currently among of the chief methods in dealing with patients suffering from atherosclerotic coronary heart disease. The current study aimed to measure and compare the levels of proinflammatory cytokines and oxidative stress marker in patients who underwent multivessels Minimally Invasive Coronary Artery Bypass Graft Surgery (MICS-CABG) versus off-pump Coronary Artery Bypass Grafting (off-pump CABG) in the cardiothoracic department, Assiut University hospitals, Upper Egypt. the study included 67 patients, all of them suffering from atherosclerotic coronary artery disease, which confirm by cardiac catheter angiography. The patients were divided randomly into two groups, first group (A) included 34 patients to whom Multi Vessels Coronary Artery Bypass Graft Surgery (MICS-CABG) under off pump had been done. The second group (B) included 33 patients whom underwent off pump Coronary Artery Bypass Grafting (off-pump CABG). Tumor Necrosis Factor-Α (TNF-α), interlukin-2 (IL-2), lipid peroxides, Superoxide Dismutase (SOD), total thiols and Nitric Oxide (NO) were estimated in sera of all patients by their corresponding methods; 48 h before the operation, 15 min before the operation end and 72 h after the operation. After testing the normality, Mann-Whitney U test and Spearman correlation coefficient were used to compare the two groups and tested the variables' correlations with the duration of the operation. p≤0.05 was considered significant. Serum TNF-α, IL-2 and lipid peroxides levels were significantly higher while total thiols and SOD were significantly lower, intraoperative and postoperatively, while No was significantly higher intraoperative only, in off-pump CABG group compared to MICS-CABG group and in both groups, intraoperative and postoperatively compared to preoperative levels. Especially in the postoperative samples, TNF-α, IL-2 and NO levels correlated positively while those of SOD correlated negatively with the operation duration the clinical data obtained presented in details in the result sector and revealed that. MICS-CABG group associated with less postoperative pain, less need for blood transfusion, less hospital stays and rapid regain to normal activity. The current study revealed that MICS-CABG is an effective procedure that is associated with small surgical trauma and lower inflammations and oxidative stress compared to off-pump CABG.