Anemia is a frequent hematological complication in patients with Chronic Hepatitis B (CHB), significantly impacting their overall prognosis and quality of life. The pathogenesis is multifactorial, primarily involving chronic systemic inflammation, hypersplenism secondary to portal hypertension, and impaired hepatic synthesis of hematopoietic factors. A retrospective cross-sectional study was conducted involving 100 participants. The main group comprised 70 patients with confirmed CHB presenting with anemic syndrome, while the control group included 30 healthy, age-matched individuals. Comprehensive laboratory assessments included complete blood counts, biochemical liver function tests, and iron profiles. Statistical analysis was performed using the Student’s t-test and chi-square test. The results demonstrated that patients with CHB exhibited significant hematological disruptions. The mean hemoglobin level was markedly reduced in the CHB group (94 ± 8.5 g/L) compared to controls (138 ± 10.2 g/L, p < 0.001). Additionally, concomitant thrombocytopenia (115 ± 18 x 10^9/L vs. 250 ± 22 x 10^9/L, p < 0.01) and leukopenia were prevalent, strongly correlating with signs of hypersplenism. Altered iron metabolism, characterized by low transferrin saturation (15 ± 3%) despite normal or elevated ferritin (340 ± 45 mcg/L, p < 0.01), indicated a strong component of anemia of chronic disease. Anemia in CHB is predominantly driven by hypersplenism coupled with chronic inflammatory iron sequestration. Early identification of these specific laboratory patterns is crucial for comprehensive patient management, preventing severe cytopenic complications, and optimizing antiviral therapy.