This study aimed to assess the prevalence of anemia of chronic diseases (ACD) in pa-tients with systemic lupus erythematosus (SLE) and the presence of antibodies to hu-man EPO in their sera (anti- EPO antibodies). This study included 200 patients with SLE; all underwent clinical evaluation of immunologic parameters. hemoglobin con-centration (Hb conc.) was determined. Blood samples were obtained for ELISA esti-mation of serum IL-6 and EPO levels and for ELISA testing for anti – EPO antibod-ies. hemogram detected 73 ACD patients (36.5%) with mean Hb conc. Of 106 ±0.8 gm/dl (Anemic group); the other 127 patients (63.5%) were either not anemic or had other types of anemia (NON – anemic group) with mean Hb conc. Of 12.9 ± 0.5 gm/dl. There was a negative significant correlation between Hb conc. and hematolog-ical score. mean serum IL-6 ESTIMATED in patients with SLE was 53.9 ± 19.9 ng/ml and was considerably (P-value ˂ 0.05). Mean serum IL-6 estimated in anemic group (60.9 ± 23.1 ng/ml was considerably higher compared both to control and non – anemic groups (49.8 ±16.5, P-value ˂ 0.05) ng/ml with a considerably higher levels of serum IL-6 in non – anemic SLE patients compared to controls mean serum EPO estimated patients with SLE was 21.2 ± 12.1 Miu/ml and anti-EPO antibodies (anti – EPO positive) were detected in 105 patients(52.5%) while the other 95 patients (47.5%) were negative for anti-EPO antibodies (anti – EPO Negative). mean serum – EPO level was significantly (p ˂ 0.05) lower in anti – EPO Negative patients (16.8± mIU /ML) compared to (anti – EPO positive patients (28.7 ±14 mIU /ML). MEAN serum EPO level was significantly (p ˂ 0.05) higher in anemic (28.9±16.8 mIU /ML) compared to non – anemic patients (16.7±3.8 mIU /ML) there was a Negative signifi-cant correlation (r= -0.331’ p ˂ 0.001) between presence of Anti – EPO antibodies and Hb conc; however, there was a non – significant difference between Hb conc. be-tween anemic patients with and without anti – EPO antibodies or between non –anemic patients with and without anti – EPO antibodies. there was a Negative signifi-cant Correlation between Hb conc. and serum EPO ‘ (r=-0.256 ‘ p=0.028 and IL- 6’(r= -246 ‘ p=0.036) and a positive significant correlation between serum IL- 6 and EPO ‘(r= 0.238 ‘ p=0.043) EVALUATION of specificity of estimated parameters for pathogenesis of SLE – induced anemia using ROC curve analysis judged by the area under the curve (AUC) defined IL- 6 as the most specific factor (AUC = 0.827) fol-lowed by positivity for anti EPO (AUC = 0.662) and the least specific wad EPO (AUC = 0.588).it could be concluded that the frequency of SLE – induced anemia of chronic disease was 36.5% and the presence of anti - EPO antibodies and elevated IL-6 play a complementary role in its pathogenesis.