Objective:To examine the temporal profile of absolute and lymphocyte subset data from dimethyl fumarate (DMF) start and relationships to disease behavior.Methods:A retrospective study performed on patients with an existing diagnosis of MS and a history of DMF exposure from a single MS center. Demographic, laboratory, and corresponding clinical relapse and MRI data were recorded from baseline and in 3–4-month intervals after treatment initiation extending to 3 years. The Spearman rank coefficient and mixed-effects models were used to assess longitudinal correlations between cell counts and measures of disease activity.Results:A total of 292 patients with MS (228 women; median age at DMF initiation: 40.6 years, range: 16.1–66.7 years) were identified. An increased risk of disease activity was associated with higher absolute lymphocyte count (ALC) values at 3 months (p = 0.001, OR: 1.82) and at 6 months (p = 0.032, hazard ratio: 1.73). A reduced risk of disease evolution in patients with lower ALC values < 1,200 cells/μL compared with midtier (1,210–1,800 cells/μL) and the highest tertile (>1,810 cells/μL) was observed (p = 0.01).Conclusions:Reductions in ALC values at months 3 and 6 after treatment initiation appear to be associated with improved clinical and radiologic outcomes. These data alone may help to provide a better understanding of both the safety and efficacy of DMF.