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Background: Pruritus in uremic patients decreases the quality of life because of sleep disturbances, depression and anxiety, thus, pruritus remains an important health issue in ESRD patients. Aim of the work: To evaluate the efficacy and safety of sertraline versus omega 3 supplementation in the treatment of uremic pruritus. Patients and Methods: This randomized case control study was conducted on patients with ESRD patients .All studied subjects had been collected from the Al-Azhar hospital [Damietta] Dialysis Center. This study had been carried out on 50 patients divided into: Group [A] : consists of 25patients had been received 50 mg sertraline twice a day for 8 weeks. Group [B]: consists of 25 patients and had been receive 3 gm omega-3 daily. Results: Although pruritus severity decrease significantly in both groups and both scoring systems [P<0.001], the reduction was significantly more in sertraline group [p <0.001 in VAS]. The mean pruritus score [VAS] in the omega-3 group compared with sertraline] group in pre-treatment period [5.9±1.2 vs 6.2±1.4], P < 0.001] and after 8 weeks [5.1±0.87 vs. 4.7±1.02, P < 0.001] intervention periods showed higher significant decrease in sertraline group. Conclusion: Omega-3 fatty acids found to be effective in decreasing of uremic pruritus. So, it seems that Omega-3 fatty acids could be used as an efficient drug for treatment of pruritus in uremic patients. The present study showed that lowdose sertraline was effective for antihistamine-refractory uremic pruritus than omeg3 in renal palliative care patients.