The aim of this study was to determine the effects of feeding pomegranate by-product silage on feed intake, blood metabolites, inflammatory markers, prostaglandin metabolites, serum progesterone concentration and quantity and quality of milk production in fresh Holstein cows. For this purpose, a total of 12 multiparous Holstein dairy cows were allocated randomly to 2 treatments with 6 replicates each. The cows entered to experiment after the parturition and left on day 15 after estrous cycle synchronization (about day 90 postpartum). The treatments were: 1- Control group and 2- Group fed pomegranate by-product silage. In the ration of experimental group, corn silage was replaced by pomegranate by-product silage (12% of total dry matter). Cows fed total mixed rations (TMR) formulated according to the high producing dairy cow’s requirements. Feed intake was weighed twice a week. Blood samples were collected from tail vein on 0, 7, 14, 21 and 28 d postpartum. The serum metabolites such as non-esterified fatty acids (NEFA), beta-hydroxy butyrate (BHBA), malondialdehyde (MDA) and the inflammatory markers (i.e. interleukin-1 and amyloid-A serum) were determined in blood sampels. For prostaglandin metabolites (PGFM) determination, the estrous cycle of all cows was synchronized using the modified Heatsynch protocol, then cows were i.m. injected (100 IU (of oxytocin on day 15 of the estrous cycle and after that blood samples were collected at 1 h before and 3 h after oxytocin injection with 30 min intervals. In order to monitoring of ovarian activity using serum progesterone (P4), blood samples were collected every 3 days during the 14 to 35 d postpartum. The ovarian status was evaluated by ultrasound on day 25 postpartum. Milk samples were collected monthly from the 3 consecutive milking a day (morning, afternoon and night). The results showed that Feed intake decreased slightly and there was no significant difference. Feeding pomegranate by-product silage had no significant effect on NEFA concentrations at sampling days and during the entire period. But, it decreased blood serum BHBA concentration on days 7 (P 0.02), 21 (P 0.05) and entire sampling period (P 0.01). Moreover, it tended to be significant on day 28 (P 0.06). The MDA concentration was significantly lower in cows fed pomegranate by-product silage compared with control group in days 7 (P 0.03), 14 (P 0.03) and 28 (P 0.004) postpartum. The concentration of PGFM was numerically lower in cows fed pomegranate by-product silage group while this effect was not statistically significant between treatments (P 0.48). The IL-1 concentration changes during entire period (P 0.03) and on day 28 postpartum (P 0.01) was significant. Likewise, the interaction of treatment and time was observed (P 0.001), so that the highest concentration of IL-1 was in the control group on day 21 postpartum. The concentration of SAA was numericallydeclined but there was no significant difference between the treatments. Feeding pomegranate by-product silage result numerically increased the serum progesterone (P 0.44). On the other hand, cows fed pomegranate by-product silagehad more active ovaries and more yellow bodies on day 25 postpartum compared with the control group. Feeding pomegranate by-product silage had no effect on milk yield, percentage and total of milk protein. But, the percentage of milk protein was tended (P 0.06) to be significant at the end of first month of lactation by feeding pomegranate by-product silage. In general, these results show that feeding pomegranate by-product silage improved some blood metabolites associated with energy balance and the inflammatory response in fresh dairy cows. Keywords : Holstein cow, Pomegranate, Blood metabolite, Inflammation, Milk production