This study was conducted to determine bovine mastitis resistance genes of common etiological agents in Al-Sharkia province. In addition to monitor the changes in antioxidants profile, oxidative stress status and some of biochemical markers in dairy cows suffered from clinical mastitis. It was carried out on forty dairy cattle (40) aged from 4 – 6 years (20 healthy and 20 mastitic) from dairy farms and individual cases in Al-Sharkia Governorate, dependent on the findings of the clinical examination, the cattle were divided into 3 groups. Gp1 healthy dairy cattle (control), Gp2 mastitic dairy cattle before treatment, Gp3 mastitic dairy cattle after treatment. The clinical symptoms of mastitis including milk and udder were reported in Gp2. Within the bacterial isolates (20) it was noticed that the highest spread was of Staphylococcus aureus (10) followed by E.coli (6) and Klebsiella Spp. (4). Antibiotic sensitivity test displayed that gentamycin, streptomycin were the more sensitive antibiotics for S. aureus, E.coli and Klepsiella. While amoxicillin and clavulanic acid, tetracycline, florfenicol and cefotaxime were the more resistant antibiotics. Enrofloxacin was moderate sensitive in s. aureus and E.coli while more resist in Klebsiella. Real time PCR assay was used for detection of antimicrobial resistance genes. Eleven isolates representing, 5 S. aureus, 3 Klebsiella and 3 E.coli were selected for detection of multi drug resistant (MDR) genes. The blaTEM gene was detected in all isolates of S. aureu, E. coli and 2 isolates of Klebsiella. While, the tetA gene was detected in 4 out of 5 isolates of S.aureus and all isolates of E.coli and Klebsiella. Moreover, floR gene was detected in 3 isolates of S.aureus, 2 isolate of E.coli and all isolates of Klebsiella. Biochemically, there were significantly increases in serum AST, ALT, ALP, urea, creatinine, Na, Mg, NO, PH, beta 1, total beta, total globulin and milk MDA associated with non-significant increases in t.protien, alpha 1, total alpha, gamma 1, gamma 2 and total gamma. Meanwhile, there were a significant decrease in serum Cl, Ca, K, TAC, beta 2, A:G ratio and milk SOD, CAT, GSH, associated with non-significant decrease in alpha 2. On the other hand, there were significant increases in serum albumin, immune-globulin and other proteins in whey milk, meanwhile, there were a significant decrease in α–lactoglobulin and ß- lactoglobulin in whey milk in mastitic group when compared with normal healthy cows. The results of the current investigation suggested that the body antioxidant defense system was compromised in dairy cows with clinical mastitis generating a state of oxidative stress.