Background Critically ill traumatic brain injury (TBI) patients experience extensive muscle damage during their stay in the intensive care unit. Neuromuscular electrical stimulation (NMES) has been considered a promising treatment to reduce the functional and clinical impacts of this. However, the time needed for NMES to produce effects over the muscles is still unclear. This study primarily aimed to assess the time needed and effects of an NMES protocol on muscle architecture, neuromuscular electrophysiological disorder (NED), and muscle strength, and secondarily, to evaluate the effects on plasma systemic inflammation, catabolic responses, and clinical outcomes. Methods We performed a randomized clinical trial in critically ill TBI patients. The control group received only conventional physiotherapy, while the NMES group additionally underwent daily NMES for 14 days in the lower limb muscles. Participants were assessed at baseline and on days 3, 7, and 14 of their stay in the intensive care unit. The primary outcomes were assessed with muscle ultrasound, neuromuscular electrophysiology, and evoked peak force, and the secondary outcomes with plasma cytokines, matrix metalloproteinases, and clinical outcomes. Results Sixty participants were randomized, and twenty completed the trial from each group. After 14 days, the control group presented a significant reduction in muscle thickness of tibialis anterior and rectus femoris, mean of - 0.33 mm (- 14%) and - 0.49 mm (- 21%), p < 0.0001, respectively, while muscle thickness was preserved in the NMES group. The control group presented a higher incidence of NED: 47% vs. 0% in the NMES group, p < 0.0001, risk ratio of 16, and the NMES group demonstrated an increase in the evoked peak force (2.34 kg/f, p < 0.0001), in contrast to the control group (- 1.55 kg/f, p < 0.0001). The time needed for the NMES protocol to prevent muscle architecture disorders and treat weakness was at least 7 days, and 14 days to treat NED. The secondary outcomes exhibited less precise results, with confidence intervals that spanned worthwhile or trivial effects. Conclusions NMES applied daily for fourteen consecutive days reduced muscle atrophy, the incidence of NED, and muscle weakness in critically ill TBI patients. At least 7 days of NMES were required to elicit the first significant results.