Background: Mycophenolic acid (MPA), an efficient immunosuppressive medication used in SLE, is glucuronidated by UGTs into an inert 7-O-glucuronide. Studies have shown that the -275T>A and-2152C>T SNPs in the UGT1A9 promoter region are associated with greater hepatic production of UGT1A9 and higher MPA in vitro glucuronidation activity. Subjects and Methods: patients were selected from outpatient Clinics of Rheumatology and immunology department, UGT1A9 -275T>A and-2152C>T (SNPs) were genotyped in 50 SLE Egyptian patients and 100 healthy controls using PCR-RFLP. In addition, MPA serum concentrations were measured in patients by homogeneous particle enhanced turbidimetric inhibition immunoassay (PETINIA) technique. Results: UGT1A9-2152C>T and -275T>A distribution of genotypic analysis in SLE patients and controls revealed that the -2152C>T mutation is present in 14% patients and 21% of the control group (P = 0.3), whereas the -275T>A mutation is present in 50% of patients and only in 11% of the control group (P = 0.001). In comparison to the (TT) genotype, the combined (TA+AA) genotype exhibited significant correlation with greater GIT symptoms (68% versus 5%, respectively, P = 0.001). In SLE patients taking MPA with CT+TT genotype against CC genotype, -2152C>T mutations revealed a higher incidence of anemia (85.7% versus%, 30.2 respectively P =0.009). Both SNP genotype carriers had statistically lower C0 MPA values compared to non-carriers (1.25 umol/L (0.62-7.8) versus 4.68 umol/L (0.62-25.9), P = 0.028. Conclusion: Carrier of both UGT1A9-2152C>T and -275T>A SNPS is associated with lower C0 MPA in comparison to non-carrier in Egyptian SLE patients.