Background: Systemic Lupus Erythematosus (SLE) is a chronic auto-immune disease with diverse manifestations, ranging from mild rash or arthritis to severe organ-threatening involvement. Objective: The aim of the work was to find-out the possible association of hypophosphatemia and hyponatremia with disease activity in SLE patients. Patients and methods: A total of 100 patients with SLE were involved in this study and the serum level of sodium and phosphorus, erythrocyte sedimentation rate (ESR), leucocytic and platelet counts, and 24 hr. protein were measured. SLE disease activity index (SLEDAI) score was assessed, Results: The majority of patients were females; 94 (94%) and 6 males (6%) (F:M 15.7:1). The age of the patient ranged from 17 to 63 years with a mean age of 34.23 ±11.19 years. The disease duration was 48±55.7 months. 7. 41% of SLE patients were hyponatremic and 49% showed normonatremic. There was a significant correlation between Na level, SLEDAI score, vasculitis and arthritis and insignificant correlation with ESR. 47 patients were hypophosphatemic (47%) and 53  (53%) were normophophatemic. There was a significant correlation between phosphate level and SLEDAI, oral ulcers p=0.001 and arthritis p < 0.0004 but negatively related with ESR. Conclusion: It could be concluded that hyponatremia and hypophosphatemia are significantly related to SLEDAI, so it could be used as indicators of SLE activity and sever inflammation.