High feed costs and compromised meat quality are among the major issues perturbing the global broiler industry. This study therefore investigated Vachellia erioloba pods-derived oyster mushroom spent substrate (OMSS) as a potential nutraceutical feed ingredient to replace wheat bran for enhancing meat quality in broilers. Four hundred male Ross 308 chicks at 14 d of age were randomly allocated to 40 pens and fed treatment diets (0%, 1.25%, 2.5%, 5% and 10% OMSS) each with 8 replicates of 10 birds for 28 d (grower: d 15 to 28, and finisher: d 29 to 42) prior to slaughter on d 43. Whilst there were no effects of diet on overall body weight gain (BWG), feed conversion efficiency (FCE), mortality rate, carcass traits, meat physicochemical quality, and most haemato-biochemistry parameters (P > 0.05), dietary OMSS increased chicken overall feed intake (FI) (linear: P = 0.043), gizzard weights (linear: P = 0.021), and breast meat ether extract (EE) (linear: P < 0.001) as it tended to increase its ash (P = 0.064) contents. Further, OMSS linearly increased chicken white blood cells (P = 0.044), lymphocytes (P = 0.002), platelets (P = 0.009), monocytes (P = 0.007), and lipase activity (P = 0.015), and linearly decreased its eosinophils (P = 0.007) and platelet distribution width (PDW; P = 0.003). Moreover, OMSS increased breast meat myristic (linear: P = 0.012), palmitic (quadratic: P = 0.015), palmitoleic (linear: P = 0.023), and oleic (linear: P = 0.002) acids, and impacted its total monounsaturated fatty acids (MUFAs), with 1.25% and 5% inclusion levels inducing the lowest and highest responses, respectively (P = 0.024). In contrast, it decreased meat stearic (linear: P = 0.004), eicosenoic (linear: P = 0.004) and eicosadienoic (linear: P = 0.025) acid contents. However, OMSS did not affect meat's vaccenic, linoleic, alpha-linolenic, eicosatrienoic, total saturated fatty acids (SFAs), polyunsaturated fatty acids (PUFAs), n-3 PUFAs, n-6 PUFAs, and n-6/n-3 PUFA ratios (P > 0.05). In conclusion, dietary OMSS replacement of up to 10% wheat bran increased broiler meat fatness, ash, and MUFAs, as well as immune competence, lipase activity, gizzard weights and FI without altering other performance variables, carcass-visceral traits, haemato-biochemistry, and meat physicochemical quality. (c) 2025 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).