This research was designed to appraise the single or combined effects of dietary sodium butyrate (SB) and sodium propionate (SP) on growth, serum biochemical parameters, serum and skin mucus immune responses, and expression of immune-related genes in goldfish fry. To design seven experimental groups in triplicates, the fry (n = 315; 5.6 +/- 0.1 g) were randomly stocked in 21 tanks (150 L) with a density of 15 fish per tank. In this study, a basal diet (36.81% crude protein, 11.33% lipid, and 3.5% ash) was considered as the control diet and the other experimental diets were formulated by adding SB 0.1% (SB1), SP 0.1% (SP1), SB 0.2% (SB2), SP 0.2% (SP2), SB 0.1% + SP 0.1% (SB1SP1), and 0.2% SB + 0.2% SP (SB2SP2) into the basal diet. The fish were fed ad libitum with the corresponding diets three times per day for 56 days. The current study was measured the serum biochemical and immune parameters, mucus immunity, and the expression of immune-related genes using the blood, mucus, and head kidney samples, respectively. After 56 days, the highest growth rate (2.85 +/- 0.04%/day) and the lowest feed conversion ratio (1.65 +/- 0.06) were recorded in SB2SP2 treatment (p < 0.05). The serum lysozyme activity enhanced 1.76 folds in the fish fed with SB2SP2 diet compared to the control group (p < 0.05). Moreover, the highest skin mucus lysozyme activity (17.52 +/- 1.40 U/mL) was observed in B2SP2 treatment, which showed a 1.69-fold increase compared to the control groups (p < 0.05). Total immunoglobulin levels in the serum and mucus samples of the blended acidifier-supplemented diets were significantly higher than the control group (p < 0.05). The levels of serum alanine aminotransferase, aspartate aminotransferase, glucose, and cortisol significantly decreased in all treated fish compared to the control fish (p < 0.05). The relative transcription levels of tumor necrosis-alpha, lysozyme, interleukin-1 beta, and interleukin-8 genes were significantly upregulated in SP2SB2 group compared to the control group. The results of the present study revealed the beneficial synergistic effects of dietary SB and SP, especially at 0.2%, on the growth performance, physiological responses, and immunity of goldfish.