Purpose To examine the acute and chronic effects of 10-weeks of progressive resistance training on sleep quality and sleeping heart rate variability in persons with Multiple Sclerosis (pwMS). Methods Eighteen pwMS (age = 44.8 ± 10.6 years; EDSS = 3.1 ± 1.7) completed a 10-week of resistance training, with three training sessions per week. Each session consisted of 4 lower body exercises, performing 2–4 sets of each exercise, with 8–15 repetitions each set, at an intensity ranging from 60 to 75% of 1-repetition maximum. Subjective and actigraphic sleep quality and sleeping heart rate variability were carried out at 4 different times: (1) Before the starting of the intervention on a rest day; (2) the night after training week 1 (3) the night after training week 10 and 4) after completing the resistance training program on a rest day. Results Regarding subjective sleep quality, significant main effects were observed on the variables of sleep quality, sleep comfort, easy of falling sleep, easy of waking up and felling of rest. Sleep quality, sleep comfort and easy of falling sleep were greater in rest night in week 1 vs. rest night in week 10. Actigraphic sleep quality also improved after the training program (rest night in week 1 vs. rest night in week 10). In the pair-wise comparison showed an acute effect in the session after the training program (rest night in week 10< training night in week 10) on HF, pNN50 and RMMSD. Conclusions Resistance training is a non-pharmacological treatment that has the capacity to improve the regulation of autonomic system and, consequently, the sleep quality in pwMS. Implications for rehabilitation 10 Weeks of resistance training improves the sleep quality of persons with multiple sclerosis. Resistance training can modulate autonomic cardiac control in this population. Improving the sleep quality is essential for persons with MS because of its close relationship to other variables, such as symptomatic fatigue.