Infection is a cause of high morbidity and mortality in myeloma. The aim of this study was to identify risk factors for the occurrence of infection in patients treated for multiple myeloma in the clinical hematology department at Dalal Jamm Hospital. A case–control study was conducted from January 1, 2005, to April 30, 2024. Each patient was matched with a control of the same sex and age ± 2 years. Patient diagnosed with myeloma according to International Myeloma Working Group criteria and who had an infection was considered a case, and controls were myeloma patients without infection. Data were analyzed using SPSS Statistics version 25 software. A p-value < 0.05 was considered significant. The Shapiro test was used to test for normality in the distribution of variables. Pearson correlation was used to determine the strength of association. One hundred and eight (108) cases and 80 controls were included, with a median age of 61.1 ± 9.67 years for cases and 62.15 ± 11.39 years for controls. The sex ratio was 1.25 and 1.05 in cases and controls, respectively. Infection was predominantly pulmonary (50%) and urinary (30%). Median survival was 1.2 years for cases and 2.6 years for controls. In multivariate analysis, risk factors for infection were a Charlson comorbidity score ≥ 1 (p = 0.006; OR = 2.39; CI: [1.247–4.599], positive CRP (p = 0.0040; [OR = 0.473; CI 95%: [0.231–0.966]), renal failure (p = 0.045; [OR = 2.263; CI95%: [0.210–24.342]) and type of treatment. The risk factors identified in our study were the presence of comorbidity, a positive CRP, the presence of renal failure and the treatment.