The present trial investigates the effects of soil-derived Streptomyces chartreusis KU324443 as a probiotic on growth performance, mucosal and serum immune parameters, and immune and antioxidant-associated gene expression in common carp (Cyprinus carpio). In a two-month experiment, carps were fed with varying levels of S. chartreusis KU324443 (0 (control), 105 (S1), 106 (S2), and 107 (S3) CFU/g). Then, performance, skin mucus, and serum immune parameters besides immune and antioxidant-related gene expression (IL1 and Lyz, CAT and SOD) were measured. Fish fed S. chartreusis-supplemented diet showed a significant increase in growth performance parameters (
P
<
0.05
) regardless of inclusion levels. Including different doses of S. chartreusis significantly increased serum total Ig and lysozyme activity compared to those fed the control diet (
P
<
0.05
). While no significant difference was noticed in the case of skin mucus total Ig (
P
>
0.05
), lysozyme activity showed a significant increase in S. chartreusis-treated carps (
P
<
0.05
). No significant differences (
P
>
0.05
) were noticed in the case of serum antioxidant enzyme activity (CAT, SOD, and GPx) of S. chartreusis-fed carps and control. However, fish fed the control diet recorded the highest SOD and GPx enzyme activity in skin mucus of common carp, while no significant differences were noticed in the case of mucus CAT enzyme activity in common carp (
P
>
0.05
). Gene expression studies revealed noticeable alterations between treated fish and control. Fish in S3 treatment had significantly higher CAT, SOD, Lyz, and IL1 expression (
P
<
0.05
). These results confirmed the beneficial effects of a soil-derived probiotic (S. chartreusis) on the performance and health of common carp.
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