The objective of this study was to evalute the effect of feeding dietary cation-anion difference during peripartum period on hematological, immunological, and proinflammatory markers in periparturient Holstein-Friesian cattle. Blood samples were collected from 36 periparturient multiparous Holstein-Friesian cows where 18 cows were fed acidogenic diet daily low dietary cation-anion difference (L-DCAD group) 21 day before calving, and 18 cows fed normal diet (control). Feeding acidogenic diets during pre-partum period caused leukocytosis and lymphocytosis and significant increase (P<0.05) in cortisol and CRP concentration during pre-partum and post-partum periods, and IL-6, IgA and IgG concentrations during the post-partum period. The liver function tests showed significantly increase in GOT, GPT, GGT and ALP in cows feed dietary cation-anion difference (DCAD) compared to control. We concluded that feeding acidogenic diets during pre-partum period on a low DCAD diet might induce immunologic, hepatic and inflammatory changes that may represent further stress to periparturient dairy cattle