Objectives of the study were to compare the effects of a single bout of preventive or regenerative foam rolling (FR) on exercise-induced neuromuscular exhaustion. Single-centre randomised-controlled study was designed. Forty-five healthy adults (22 female; 25±2 yrs) were allocated to three groups: 1) FR of the lower limb muscles prior to induction of fatigue, 2) FR after induction of fatigue, 3) no-treatment control. Neuromuscular exhaustion was provoked using a standardized and validated functional agility short-term fatigue protocol. Main outcome measure was the maximal isometric voluntary force of the knee extensors (MIVF). Secondary outcomes included pain and reactive strength (RSI). Preventive (-16%) and regenerative FR (-12%) resulted in a decreased loss in MIVF compared to control (-21%; p < 0.001) five minutes after exhaustion. Post-hoc tests indicated a large-magnitude, non-significant trend towards regenerative foam rolling to best restore strength (Cohen’s d > 0.8, p < 0.1). Differences over time (p < 0.001) between groups regarding pain and RSI did not turn out to be clinically meaningful. A single bout of foam rolling reduces neuromuscular exhaustion with reference to maximal force production. Regenerative rather than preventive foam rolling seems sufficient to prevent further fatigue.

• Foam rolling directly affects muscular structures following exhaustion.

• The effects are independent of the time of intervention (whether pre or post to the load).

• Regenerative foam rolling seems adequate to elicit beneficial effects.

• Foam rolling could be helpful in preventing sports-related muscular injury.