It has consistently been demonstrated that disuse models (e.g. limb immobilisation and bed rest), result in skeletal muscle atrophy, decreases in maximal voluntary strength (1) and bone mineral density (2), and increases in intermuscular adipose content (3). Disuse models have also been associated with changes in electromyography (EMG) characteristics (4) and muscle fatigability (1). Where exercise prescription is not possible (e.g. bed rest or injury), other interventions are required to attenuate these changes associated with disuse. Non-pharmacological interventions need to be identified since polypharmacy in itself is conducive to skeletal tissue loss (5). This study set out to determine whether two potential protein-sparing modulators (eicosapentaenoic acid [EPA] and vitamin D [VitD]) would modulate the deleterious effects of immobilisation. The non-dominant arm of 24 healthy participants, aged 23.0±5.8 years, was immobilised in a sling for a period of 9 waking hours a day over two continuous weeks. Participants were randomly assigned to one of three groups: placebo (PLA) (n=8), EPA (n=8) or VitD (n=8). Body composition (DEXA), arm girth (anthropometry), muscle co-contraction (EMG) and muscle fatigability (Cybex and EMG) were measured before, at the end of the immobilisation period and two weeks after re-mobilisation. The effect of immobilisation and supplement group were assessed by either repeated measures ANOVA (parametric data), with post-hoc Bonferonni corrected 2-tailed t-tests or Kruskal Wallis test (non-parametric data), with post-hoc Mann-Whitney U tests. All data are presented as mean ± standard deviation. There were significant decreases in upper and lower arm girth, lean mass and bone mineral content (BMC) post-immobilisation in the PLA group (p<0.05). Despite no significant effect of group, EPA and VitD supplementation showed trends towards attenuating the decreases in upper/lower arm girths (-1.3±0.4% PLA, -0.6±0.5% EPA, -0.9±1.0% VitD, p=0.18 and -0.8±0.8% PLA, -0.4±0.5% EPA, -0.3±0.4% VitD, p=0.21, respectively) and BMC (-2.3±1.5% PLA, -0.3±1.0% EPA, -0.7±1.9% VitD, p=0.47) observed in the PLA group. The EPA supplementation group demonstrated a non-significant attenuation of the decrease in lean mass observed in the placebo group (-3.6±3.7% PLA, -1.9±2.8% EPA, -4.0±2.8% VitD, p=0.95). There was no significant change in muscle fatigue parameters or EMG co-contraction values with immobilisation and no effect of supplementation group (P>0.05). All parameters had returned to baseline values at the re-mobilisation phase of the study.​ The results suggest that both EPA and VitD may generally attenuate the changes in muscle size and bone parameters associated with immobilisation. These findings may be applicable to both sporting (e.g. off-season detraining) and clinical (injury/surgery induced short-term immobilisation) populations.