e23215 Background: Infectious complications are the leading cause of morbidity and mortality in patients with chronic lymphocytic leukemia(CLL) and multiple myeloma(MM). Despite recognized risks, evaluation of immune function occurs inconsistently. Our retrospective study evaluated practice patterns for assessing secondary immunodeficiency (SID) in newly diagnosed CLL and MM patients. Our aim is to identify areas for improvement to guide future prospective studies. Methods: We analyzed various immune parameters in newly diagnosed CLL and MM patients at Rochester Regional Health, Rochester, NY, focusing on the first six months of their clinical course, with descriptive data analysis. Results: Conclusions: Current infection prevention guidelines for newly diagnosed CLL and MM patients lack robust evidence. Despite our study’s inherent limitations (small, retrospective, single-center), based on our clinical experience, we propose the following recommendations: Complete SID assessment in all new diagnoses of CLL and MM, and this should include not only Ig levels but also vaccine response. If found to have abnormal SID evaluation, consider prophylactic antibiotics and Ig replacement, and consider reevaluation when appropriate to better define the duration of immunoparesis. Consider short-term Ig replacement (irrespective of IgG levels) and antibacterial prophylaxis for all newly diagnosed MM patients due to high infection risk during the initial six months. A thorough immune evaluation is non-invasive and low-cost, yet it can reveal clinically significant immune dysfunction, potentially influencing management in CLL and MM. Consequently, we hope our study will prompt the development of prospective, randomized studies to systematically evaluate these recommendations. [Table: see text]