This case report highlights a rare but significant complication associated with the use of granulocyte-colony stimulating factor (G-CSF) therapy, specifically splenic infarction, in a 67-year-old male with chronic myelomonocytic leukemia (CMML) undergoing chemotherapy. G-CSFs, such as Neulasta (pegfilgrastim), are frequently used to prevent febrile neutropenia in cancer patients undergoing myelotoxic chemotherapy. While G-CSF is effective in reducing the risk of neutropenia, its administration has been linked to uncommon but severe complications like splenic infarction and rupture. Our patient, receiving dose-dense chemotherapy with G-CSF support, developed severe abdominal pain midway through treatment. A computed tomography (CT) scan revealed multiple splenic hypodensities consistent with splenic infarction, but no active bleeding. Conservative management was successfully employed, avoiding surgical intervention. This case underscores the need for vigilance when administering G-CSF, particularly in patients at high risk for complications, and contributes to the limited body of literature on G-CSF-induced splenic infarction.