Rumen cannulated Nellore bulls (n = 4) were used in a 4 × 4 Latin square design, with a 2 × 2 factorial scheme to evaluate the effects of vitamin supplementation on: (1) ingestive, digestive, and ruminal parameters; (2) serum concentrations of 25-hydroxyvitamin D (25(OH)D); and (3) in situ degradability of complete diets. The factors consisted of two fat-soluble vitamin blend (ADE) supplementation levels (ADE− or ADE+) and two B vitamin blend (biotin, niacin, and thiamine) supplementation levels (B-blend− or B-blend+). Thus, the treatments evaluated consisted of no vitamin supplementation (ADE− B-blend−), supplementation of a B vitamin blend (ADE− B-blend+), supplementation with a fat-soluble vitamin blend (ADE+ B-blend−), or a combination of these two blends (ADE+ B-blend+). Nutrient intake and DM, as well as ruminal digestibility were not affected (P > 0.05) by any of the vitamin supplementations. The apparent total-tract digestibility of DM, organic matter (OM), neutral detergent fiber corrected for residual ash and protein (apNDF), crude protein (CP), and non-fiber carbohydrates (NFC) were not influenced by the experimental diets (P > 0.05). Furthermore, an increase in starch total-tract digestibility was verified with ADE supplementation in the diets (P = 0.031). None of the in situ parameters were affected (P > 0.05) by vitamin supplementation. Further, the treatments did not affect ruminal kinetics (ki, kp, and kd,) of DM, OM, and starch (P > 0.05). The omasal flow of total N, NH3-N, non-ammonia N, microbial N, and non-ammonia non-microbial N (P > 0.05) or the efficiency of microbial protein synthesis (P > 0.05) were not affected by vitamin blend supplementation. The total fat volatile acid (VFA) concentrations, as well lactate concentration were not affected (P > 0.05) by vitamin blend supplementation. Bulls that consumed the combination of ADE and B-blend supplementation had lower ruminal NH3-N concentrations (P = 0.008). B-blend vitamin supplementation decreased ruminal pH (P = 0.003). As expected, concentrations of serum 25(OH)D increased (P = 0.001) in Nellore bulls fed diets with the combination of fat-soluble vitamin (ADE) and B-blend supplementation. Supplementing Nellore bulls with a vitamin blend containing 25(OH)D3 was a successful strategy for increasing circulating concentrations of 25(OH)D. The B vitamin blend (biotin, niacin, and thiamine) supplementation did not improve ruminal fermentation, ingestive or digestive parameters. However, the fat-soluble vitamin blend (ADE) supplementation increased total-tract starch digestibility.