BACKGROUND: Repetitive head impacts related to soccer heading might lead to long-term risk of neurodegenerative diseases. Helping to stabilise the head-neck-torso complex could be a preventive strategy. This study aims to investigate head acceleration and heading-related acute electrophysiological and cognitive changes in soccer players, with a custom-made mouthguard (CM-MG) and without. METHODS: In this crossover study, 18 amateur male soccer players (age 22 ± 3 y) performed ten consecutive headers from machine-projected balls, with and without a CM-MG. Head accelerations during heading were recorded. Peak force of neck muscles were assessed. Before and immediately after heading, cognitive function was assessed, and the cortical silent period (cSP) was measured from the motor-evoked potentials recorded using Transcranial Magnetic Stimulation. FINDINGS: A decrease of 6·40 g (95% CI [-11·74; 39·09]) of mean peak linear head acceleration was found with the CM-MG (26·43 g) compared to without (34·15 g, p = 0·01). The peak force of the head flexor muscles was higher with the CM-MG (172 N) than without (146·7 N), with a mean difference of 19·33 N (95% CI [13·39; 25·27]) (p < 0·001). The difference in mean cSP between pre- and post-heading decreased statistically significantly with the CM-MG (-9·17 ms) compared to without (20·03 ms; p = 0·0016), with a median difference of -22·87 ms (95% CI [-45·85; -4·02]). There was also a decrease in the changes to memory performance with the CM-MG versus without. INTERPRETATION: A CM-MG may have the potential to protect the brain during soccer heading. More studies are still needed to confirm its benefits in all playing conditions on the field. FUNDING: This research received two grants from LabEx BRAIN- Bordeaux University and France Traumatisme Cranien (public sector).< Réduire