The study was conducted to evaluate the health status, blood metabolites and production performance in multiparous Holstein cows fed different amount of OmniGen-AF^® (OG; Phibro Animal Health, Quincy, IL) from dry-off (60 d before parturition) till 35 DIM (days in milk). Based on parity, somatic cell count (SCC) and expected calving date, 48 multiparous cows were assigned to 3 treatments: OG was fed 0 g/hd/d (CON), 60 g/hd/d (OG60; recommended value), or 90 g/hd/d (OG90). The supplement was added from d −60 to 28 DIM, and removed from all treatment groups during 29–35 DIM. Blood samples were collected (at 0800 h) on d −60, −28, −14, −7, 1, 7, 14, 28, 32, 35; milk parameters were tested every 7 d, and DMI was condensed to weekly means. A mixed-effects model with repeated measures was used for the analysis of the whole experimental data (DMI, blood metabolites and milk components) and generalized linear model was used for the analysis of data at each sampling point. The results indicated that OG supplementation reduced the number of cows in mastitis (P < 0.01). During the OG feeding period, serum albumin declined (P < 0.05), globulin increased (P < 0.01) and plasma nonesterified fatty acids tended to decrease (P = 0.083) in groups fed OG compared with CON. Plasma β-hydroxybutyrate concentration in OG90 group was higher than CON (P < 0.05) in the OG feeding period. Plasma haptoglobin in CON group was higher than that of OG90 on d −14 (P = 0.053) and d 1 (P = 0.019). Serum calcium content in CON group was higher than that of OG60 and OG90 on d 28 before expected parturition (P < 0.05), and lower (P < 0.05) on 7 DIM. During the postpartum period, no differences were observed in DMI and milk components. The 4% fat-corrected milk (FCM) yield in OG90 group was higher than that of CON (P < 0.05) on d 1 and in wk 1 after delivery. The SCC was decreased by OG in the first 4 wk of lactation (P < 0.01). While SCC in OG groups increased to the similar level as CON group when OG was removed during 29–35 DIM. In conclusion, OG supplementation reduces SCC in milk, improve the blood biochemical indexes associated with parturition, while it has no significant effect on DMI and milk parameters.