Background and aim: There are limited and confidante data about the effect of antiepileptic drugs in liver function. The aim of this study is to assess of carbamazepine, sodium valproate and phenytoin on plasma liver enzymes in epileptic Sudanese patients. Methods: This is an analytical case control study, conducted at National Center for Neurological Diseases and Sciences, Omdurman, Bahri and Academic Teaching Hospitals. A total of 64 epileptic patients were categorized into two groups, group I epileptic patients on antiepileptic drugs for more than one years and group II newly diagnosed epileptic patients and not started antiepileptic drugs. Analysis of AST, ALT, ALP activate and TP, Alb concentration was done by full automated machine. Results: The study showed that among group (I) there was significant increase in mean serum concentration AST 41.4±33.7, ALT 24.8±12.65 with (p-value 0.975 and 0.016) respectively, compared with mean values of control (II) who reported AST 41.2±20.5, ALT 16.8±9.66. There was significant decrease in mean plasma concentration of ALP (62.4±39.9) in Group (I) compared with mean values in group (II) (76.1±32.5) (p-value 0.137). Significant decrease in mean plasma albumin concentration 3.89±1.01 in group (I) in contrast to group (2) 4.55±1.05 (p-value 0.014). No significant change in total protein 7.36±1.08, total bilirubin 0.91±0.84, direct bilirubin 0.17±0.09, between the two groups (T.B0.63±0.49), (D.B0.18±0.12). Conclusion: The study revealed that antiepileptic drugs had significant effects in increasing liver enzymes and this necessitate continuous screening of liver function and do of drug monitoring test among epileptic patients to overcome the adverse effects of these drugs on liver.