Objective: The frequency of the HLA class II antigens (HLA DR, DQ and DP) were determined among Malay patients with systemic lupus erythematosus (SLE) to ascertain the role they play in disease susceptibility. Study design: Fifty-six Malay SLE patients on follow-up at the SLE Clinic of the National University of Malaysia Hospital, Kuala Lumpur were enrolled into the study. Controls were taken from healthy unrelated individuals, ethnically-matched. Materials and Methods: Five ml of anticoagulated blood was taken from each patient and control and DNA extracted. The HLADR, DQ and DP antigen/allele frequencies were determined by the technique of modified PCR-RFLP and statistical analysis done by Chi-square and Fischers exact test. Relative risk was determined by the odds ratio and significant p values were corrected for the number of antigens/alleles tested. Results: We found that the DR2 antigen was significantly increased among the patients (85.7%) as compared to controls (61%)(p corr=0.03, RR=3.83). As for HLA-DQA1, the allele most commonly found among the patients was *0102 (57 vs 49.2%). HLA-DQA1* 0601 was slightly decreased among the patients but this finding was insignificant. Both HLA-DQB1*0501 and 0601 were found to be increased among the patients even after correction of multiple comparisons made (p=0.0036, RR=4.56 and p=0.0048, RR=6.0, respectively). However, HLA-DQB1*0503 and 0301 was slightly decreased in the sle patients though not statistically significant. The frequency of HLA-DQB1*0201 was insignificantly increased among the patients. Limited studies on the DPB1 locus shows the uncertain role of this antigen in contributing to disease susceptibility. However, our analysis of the HLA-DPB1*0901 showed a slight increase among the patients as compared to controls but failed to remain significant after being corrected with number of comparisons made. All other HLA-DPB1 alleles exhibited similar frequencies between sle patients and controls. Conclusion: From this study we suggest that HLA DR2, DQB1*0501 and *0601 may be important genetic factors in conferring disease susceptibility in the Malay SLE population of Malaysia.