Fingolimod is an efficient and safe drug for treating relapsing-remitting multiple sclerosis (RRMS). In vivo, fingolimod is phosphorylated and binds to “sphingosine-1-phosphate”(S1P) receptors that are expressed in a wide range of cells, including lymphocytes. Under the effect of fingolimod, lymphocytes are retained in lymphoid tissues through the regulation of S1P1 receptors. The aim of the present study was to assess whether the degree of lymphopenia was correlated to the positive treatment response of RRMS patients with fingolimod. Data was sourced from the MSBase Registry. Patients were divided into two groups, according to the lymphocyte count on peripheral blood examination. Annualized Relapse Rate (ARR), time to first relapse and time to six-month confirmed disability progression were compared between groups. Group one consisted of 202 patients who reached 750 lymphocytes/mm3 during treatment while the comparison group two included 101 patients who never reached less than 1000 lymphocytes/mm3 in peripheral blood during the observation period. There were no differences between groups in ARR, time to first relapse or time to six-month confirmed disability progression. The degree of lymphopenia in peripheral blood was not associated to the positive treatment response of fingolimod in RRMS patients. •Fingolimod decreases the number of peripheral lymphocytes.•Levels of lymphopenia did not correlate to fingolimod efficacy.•There was no association between lymphocyte count and efficacy outcomes.•Higher levels of peripheral lymphocytes are not indicative of fingolimod failure.