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We present novel data concerning the time-course of adaptations and potential benefits of heat acclimation for people with cystic fibrosis (pwCF), who are at greater risk of exertional heat illness. A 25-year-old male (genotype: delta-F508 and RH117, forced expiratory volume in 1-second: 77% predicted and baseline sweat [Na⁺]: 70 mmol·L ^− 1), who had previously experienced muscle cramping during exercise in ambient heat, underwent 10-sessions of heat acclimation (90-min at 40°C and in 40% relative humidity). Adaptations included; lower resting core temperature (-0.40°C) and heart rate (-6 beats·min⁻¹), plasma volume expansion (+6.0%) and, importantly, increased sweat loss (+370 mL) and sweat gland activity (+12 glands·cm²) with decreased sweat [Na⁺] (-18 mmol·L ^− 1). Adaptations were maintained for at least 7-days, with no evidence of cramping during follow-up exercise-heat stress testing. These …