["The Journal of Physiology, EarlyView. ", "\nAbstract figure legend This study examined whether supine cycling exercise, with or without artificial gravity, preserves resting metabolic rate (RMR) during 60 days of head‐down tilt bed rest, and whether RMR responses align with integrated multivariate physiological adaptations. Twenty‐four healthy men were randomly assigned to a control group, a supine cycling group or a supine cycling during artificial gravity group. RMR, substrate oxidation, body composition (dual‐energy X‐ray absorptiometry/magnetic resonance imaging), muscle function and maximal cycling power were assessed before and after bed rest. Exercise during artificial gravity preserved RMR and maintained fat oxidation but did not prevent neuromuscular decline. Multivariate analyses indicate that substrate utilization and preservation of metabolically active lean compartments underpin RMR maintenance during bed rest. \n\n\n\n\n\n\n\n\n\nAbstract\nProlonged head‐down tilt bed rest induces metabolic and neuromuscular deconditioning. This study examined whether supine cycling exercise, with/without artificial gravity (AG), preserves resting metabolic rate (RMR) during 60 days of bed rest, and whether RMR responses align with integrated multivariate physiological adaptations. Twenty‐four healthy men were randomly assigned to control (C), cycling (EX) or cycling plus AG (EX‐AG). RMR, substrate oxidation, body composition (dual‐energy X‐ray absorptiometry/magnetic resonance imaging), muscle function and maximal cycling power were assessed before and after bed rest. Linear mixed models evaluated group‐by‐time effects. Principal component analysis (PCA) and sparse partial least squares (sPLS) regression examined multivariate correlates of ΔRMR. RMR responses differed between groups (interaction P = 0.029), with EX‐AG preventing the decline observed in C (EX‐AG vs. C ΔΔ = +133 kcal day−1, P = 0.017). Fat oxidation remained stable in EX‐AG but declined in C and EX. Both interventions attenuated lower‐body fat‐free mass loss, with greater preservation under EX‐AG, yet neuromuscular function deteriorated similarly across groups. Maximal cycling power exhibited a significant interaction (P < 0.001), declining in C, being maintained in EX and increasing in EX‐AG. PCA revealed two dominant axes: PC1 (25.9% variance) reflected preservation of fat‐free tissues, whereas PC2 (17.9%) captured gains in abdominal adiposity. EX‐AG participants clustered toward higher PC1 values, indicating tissue preservation. The sPLS model (r = 0.72) identified respiratory ratio changes (ΔRQ) as the dominant contributor. Exercise combined with AG preserves resting metabolism but does not prevent neuromuscular decline. Multivariate analyses indicate that substrate utilization and preservation of metabolically active lean compartments underpin RMR maintenance during unloading.\n\n\n\n\n\n\n\n\n\nKey points\n\nCycling exercise combined with artificial gravity appeared to preserve resting metabolic rate during long‐term (60 days) head‐down tilt bed rest.\nCycling with/without artificial gravity failed to prevent declines in maximal voluntary contraction or jump performance induced by 60 days of bed rest, although it preserved cycling power.\nWe show that metabolic and neuromuscular adaptations to bed rest may be partially dissociated, with artificial gravity primarily sustaining basal metabolic regulation while failing to maintain skeletal muscle contractile function.\nThe dissociation between metabolic and mechanical adaptations reported here provides valuable insight into the regulation of energy expenditure and muscle function in other contexts of severe inactivity, such as immobilization or ageing.\n\n\n"]