Introduction: Leprosy reactions occur during the course of the disease and can lead to disability. Hematologic examination by calculating the lymphocytes-to-monocytes ratio (LMR) is the potential risk factor for leprosy reactions, especially erythema nodosum leprosum (ENL). This study aims to assess the relationship between LMR as a risk factor for severe ENL in multibacillary (MB) leprosy patients at Prof. dr. I G. N. G. Ngoerah Hospital, Denpasar, Bali. Methods: This study used a case-control model with data from the medical records of leprosy patients undergoing treatment at Prof. dr. I G. N. G. Ngoerah Hospital from January 2020 - November 2023. The case group was MB leprosy patients who had been diagnosed with ENL reactions and the control group was MB leprosy patients who did not experience leprosy reactions. Blood serum was taken to analyze the LMR in both groups. Data were analyzed using SPSS version 26. Result: The mean value of LMR in the case group was significantly lower than the case group, 2.67 ± 1.13 versus 3.53 ± 0.96. Meanwhile, the cut-off point value used to categorize LMR was 2.95, with a sensitivity of 75% and specificity of 63.6%. The low LMR odds ratio (OR) was 4.5 (95%CI 1.29-16.76; p=0.015). Multivariate analysis showed low LMR for severe ENL with an adjusted odds ratio (aOR) of 4.080 (95%CI 0.352 - 47.25; p=0.260). Conclusion: Low LMR might be associated with an increased risk of ENL reaction in MB leprosy patients.