Background: Anemia is a common feature of the nephrotic syndrome that develops before the deterioration of kidney function. Depletion of iron stores (ferritin) and loss of iron binding protein (transferrin) in urine may contribute to the development of anemia, but iron replacement therapy is usually ineffective. Objectives: To investigate erythropoietin (EPO) deficiency as the cause of refractory anemia in children with the nephrotic syndrome. Methods: Forty children with primary nephrotic syndrome (20 with anemia and 20 with normal Hb) and 40 controls (20 with iron deficiency anemia and 20with normal Hb) were enrolled in the study. The nephrotic children were studied during disease activity. They included 23 steroid responsive, and 17steroid resistant cases. They were subjected to clinical evaluation, complete blood count, measurements of total serum proteins, serum albumin, serum cholesterol, blood urea, serum creatinine, serum ferritin, creatinine clearance, 24 hours urinary proteins and erythropoietin hormone assay by Immulite. Results: Serum EPO levels were significantly lower in both groups of nephrotic patients as compared to each corresponding control group despite similar Hb concentrations. NS anemia children had greater EPO levels than those without anemia (mean ± SD = 24.77 ± 1.85 versus 9.39 ± 0.47 mIU/ml; P ˂ 0.001) But their response to anemia in terms of EPO production was inappropriately low, almost four folds less than that detected in iron deficiency anemic controls (mean ± SD = 97.97 ± 10.12 mIU/ml). There was significant decrease in EPO level in steroid resistant as compared to steroid responsive patients. There was significant positive correlation between EPO level and serum albumin in both groups of nephrotic children. Both serum iron and ferritin levels were significantly decreased in anemic NS patients as compared to those without anemia. Conclusions: EPO was found to be low in NS even before the development of anemia. Other important contributing factors such as the extent of protein loss and iron deficiency help in the development of anemia, which when established, in presence of an inappropriate EPO response to anemia, will furthermore, aggravate the problem.