Myasthenia gravis can be efficiently treated with rituximab but there is no consensus regarding administration and dose schedules in this indication. No marker has yet been described to predict the clinical relapse of patients. Our objective was to identify the B cell subpopulations predicting clinical relapse in patients suffering from generalized myasthenia gravis and treated with rituximab. Clinical and biological data of 34 patients followed between 2016 and 2019 were prospectively collected every 3 months. Using multiparameter flow cytometry, we assessed the percentage in leucocytes of lymphocytes and several B cell subpopulations measured in residual disease conditions. CD19+ were also measured in non-residual disease conditions. Clinical examinations were performed by neurologists using the Osserman score. Clinical relapse occurred in 14 patients (41%). No patients required ICU or ventilatory assistance. The mean improvement of the Osserman score was 17.18 (3-45) after the first rituximab treatment (p < 0.0001). The mean delay between the first rituximab maintenance cycle and clinical relapse was 386.8 days. At the time of relapse, CD27+ increased (p = 0.0006) with AUC = 0.7654, while CD19+ did not. At a threshold of 0.01%, the sensitivity and specificity of CD19+CD27+ were 75.8% and 72.8%, respectively, and the positive and negative predictive values were 28.0% and 95.6%, respectively. The percentage of memory B cells in whole blood cells can accurately predict clinical relapse in myasthenia gravis patients treated with rituximab. This monitoring allows physicians to tailor rituximab administration and to decrease the number of infusions over time.Keywords: Myasthenia gravis; clinical relapse; memory B cells; rituximab.