Marine foods can diversify dietary protein sources and provide amino acids required for tissue protein synthesis and maintenance. Protein quality depends on both amino-acid composition and the extent to which amino acids are digested and become available following consumption.(1) Mussel powder is a food-derived marine protein source containing a broad amino-acid profile,(2) and can be produced from food-grade mussels unsuitable for fresh-market sale that would otherwise be discarded. Characterising its postprandial circulating amino-acid response contributes to understanding its nutritional quality. This analysis quantified acute changes in circulating amino-acid concentrations following mussel-powder consumption. Within a six-week double-blind randomised controlled trial, 49 adults (27 females and 22 males; median age 24 years [range 21–42]; body mass index 23.2 ± 2.7 kg/m²) were allocated to South Coast mussel powder (n = 26) or a sucrose control (n = 23). At the six-week follow-up visit, following an overnight fast and at least 24 hours after their previous dose, participants completed an acute assessment involving a supervised four-capsule dose, providing approximately 2.2 g amino acids in the mussel-powder group. Fasted finger-prick dried-blood-spot (DBS) samples collected immediately before and 30 minutes after capsule ingestion were analysed by Fatty Acid Labs (Melbourne, Australia) using isotope-dilution high-performance liquid chromatography–tandem mass spectrometry to quantify 26 amino acids.(3) Seven amino acids selected to reflect the amino-acid profile of the mussel powder were prespecified for analysis: glutamic acid, aspartic acid, lysine, glycine, leucine, arginine and alanine. DBS results were incomplete, with usable data only available pre-ingestion for 32 participants (control, n = 20; mussel powder, n = 12) and at 30 minutes for 30 participants (control, n = 16; mussel powder, n = 14). Group-by-time effects were therefore estimated using linear mixed models, with Holm adjustment across seven prespecified amino acids. Glycine, arginine and alanine data were log-transformed before analysis. From pre-ingestion to 30 minutes, geometric mean glycine was unchanged with control (253 to 252 µmol/L) but increased with mussel powder (238 to 272 µmol/L), representing a 14.6% greater relative response (95% CI 3.1% to 27.1%; unadjusted p = 0.013; Holm-adjusted p = 0.091). In the mussel-powder group, model-estimated concentrations of the remaining six prespecified amino acids increased by approximately 5%–15%, but no group-by-time interaction was significant after Holm adjustment (all, p ≥ 0.678). Although incomplete data limited conclusions regarding postprandial amino-acid availability, this study provides initial human evidence relevant to developing a convenient mussel-derived supplement for consumers who do not regularly eat whole mussels, while creating a nutritional use for food-grade mussels unsuitable for fresh-market sale.