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Highlights • Whey protein supplementation, independent of timing, increases intra cellular water and lean soft tissue. • Whey protein supplementation reduces intra and extracellular water ratio. • Resistance training increases phase angle. Abstract Aim The purpose of study was to analyze the effects of a combined whey protein (WP) and RT intervention on cellular health in pre-conditioned older women. Methods The protocol is a randomized controlled clinical trial with a sample of seventy older women, divided into 3 groups: WP-placebo (WP-PLA, n = 24), placebo-WP (PLA-WP, n = 23), and placebo-placebo (PLA-PLA, n = 23). Each group drank 35 g of product (placebo or WP) pre- and post- training. The RT program was carried out over 12 weeks (3x/week; 3 × 8–12 repetitions maximum). Total body water (TBW), intra (ICW) and extracellular (ECW) water, resistance (R), reactance (Xc), and phase angle (PhA) assessed by bioimpedance spectroscopy. Lean soft tissue (LST) was measured using dual energy X-ray absorptiometry; and food consumption was assessed by means of the average of two 24-hour recalls. ANCOVA for repeated measures was applied for comparisons, with baseline scores used as covariates. Results A group by time interaction (P < 0.05) was observed for LST, ICW and the ECW/ICW ratio. There was a time effect (P < 0.05) for TBW, Xc, and PhA. A reduction (P <0.05) in R was found only in the WP-PLA and PLA-WP groups. Conclusion Whey protein supplementation (pre- or post-) combined with RT promoted an increase in ICW and LST, and also a reduction in ECW/ICW ratio in pre-conditioned older women. Regardless of the supplementation intake, the RT regimen improved PhA in older adult women. This trial was registered at ClinicalTrials.gov: NCT03247192. [ABSTRACT FROM AUTHOR]