Background: Sickle Cell Disease (SCD) and Hereditary Spherocytosis (HS) are hemolytic diseases that produce essential changes in splenic architecture and pathophysiology. The spleen is primarily involved in removing what may be regarded as abnormal red blood cells; in these diseases, the splenic disease may well require splenectomy. Thus, splenectomy and the estimation of the changes in the spleen histopathology and hematologic status can serve as important information from the treatment perspective. Objective: To determine histopathological features of the spleen and evaluate hematologic and clinical outcomes in children with SCD and HS after splenectomy. Methodology: The present study is a retrospective cohort analysis conducted at the Histopathology Department of Nowshera Medical College, in collaboration with the Pediatric Surgery Departments of its affiliated hospitals, from January 2023 to January 2024. Altogether 151 PK pediatric patients, 95 with SCD and 56 with HS were enrolled in the study. The spleen’s histopathological changes were evaluated with the help of tissue samples, and the pre-and postsplenectomy haematologic features were compared, such as hemoglobin content, levels of reticulocytes, and transfusion rates.