Endometritis is one of the main causes of repeat breeder syndrome of cows. Sub-clinical endometritis is considered as a major contributor to the syndrome. The goal of the current study was to investigate the possible role of CPK and AST enzymes as early diagnostic parameters for detection of cows with clinical or sub-clinical endometrits and prediction of the fate of the repeat breeder cows. A total of 23 repeat breeder Holstein Friesian cows were subjected to the study. Based on clinical manifestations and the degree of uterine affections, investigated animals were subdivided into 2 groups; the severely affected cows that were assigned as the clinical endometrits group (G1, n=9), and the mildly affected cows that were assigned as the sub-clinical endometritis group (G2, n=14). Five cows from G1 and 7 cows from G2 were treated using local intrauterine Cephquenome 0.5 gm antibiotic and 4 cows from G1 and 7 cow from G2 using Lugol' Iodine 2% (30 ml) intrauterine.  The activity of CPK and AST enzymes were evaluated in both groups before and after treatment in comparison with healthy control group (n=20). In addition, protein profiles of examined animals were recorded. The results of the current study revealed that, before treatment there were up to 10 folds and 3 folds significant increase (P≤0.001) in the activity of CPK and AST, respectively, in clinical endometritis group as compared to the control healthy group. While there was up to 3 folds significant increase (P≤0.001) only of CPK activity in sub-clinical endometritis group. After treatment and occurrence of conception, significant reduction (P≤0.001) of CPK activity in both clinical and sub-clinical endometritis group and AST activity in clinical endometritis group was recorded as compared to their activities before treatment. In addition, significant elevation (P≤0.001) of total proteins and globulins levels along with significant reduction (P≤0.001) of the A/G ratio were recorded only in clinical endometritis group before treatment as compared to the healthy control group. However, after treatment, significant reduction (P≤0.001) of total proteins and globulins levels and significant elevation (P≤0.001) of A/G ratio were evident as compared to that before treatment. It was found the after using Cephquenome the conception rate in G1 and G2 was 60% (3 from 5 cows) and 85.7%       (6 from 7 cows) respectively. The resulted conception rate after application of Lugol' Iodine in G1 and G2 was 50% (2 from 4 cows) and 51.14% (4 from 7 cows), respectively. In conclusion, after exclusion of recumbency-based muscular damage, hypocalcemia or liver diseases, the activity of CPK and AST enzymes can be used as a screening parameters for diagnosis of endometrits and early detection of sub-clinical cases.