The experiment was conducted to evaluate the effect of dietary cation-anion difference (DCAD) on pH of blood and urine, mineral concentrations in serum, and hypocalcemia for sows during late gestation and lactation. A total of 22 pre-parturient sows (average parity of 4.5 ± 2.9 and BW of 224.1 ± 38.7 kg) were initially allotted to 2 dietary treatments in a completely randomized design: a control diet with positive DCAD (100 mEq/kg) and a diet with negative DCAD (−100 mEq/kg) with supplemental anionic salt (Cad-mate, Granco Minerals, Disputanta, VA) which were fed from d 93 of gestation to d 18 of lactation. Each sow had a daily access to 2 kg feed during gestation and had ad libitum access to feed during lactation. Feed with positive DCAD was provided during the subsequent parity. The pH of blood and urine were determined at d 93, 108 of gestation, d 1, 9 and 18 of lactation. At d 1 and 18 of lactation, Ca concentration in urine and milk and serum concentrations of Na, K, Mg, Ca, P, and Cl were measured. Data were analyzed using Proc Mixed of SAS with treatment as a fixed effect. Feed intake and BW loss in current lactation, and litter performance in current as well as subsequent lactations were not affected by changing DCAD. At d 1 of lactation, decreasing DCAD reduced (P < 0.05) blood pH (7.83 to 7.72). Urinary pH was reduced (P < 0.05) by decreasing DCAD at d 108 of gestation, d 1, 9, and 18 of lactation (6.18 to 5.28; 6.38 to 5.47; 6.47 to 5.10; 6.23 to 5.04). Reducing DCAD increased (P < 0.05) Ca concentrations in serum (9.23 to 9.71 mg/dL) and colostrum (66.11 to 79.34 mg/dL) at d 1 of lactation and increased (P < 0.05) serum Ca concentration (9.74 to 10.14 mg/dL) at d 18 of lactation. Reducing DCAD tended to increase Mg concentration in serum at d 1 of lactation (P = 0.097, 18.73 to 19.84 mg/L) and at d 18 of lactation (P = 0.087, 22.11 to 23.97 mg/L). At d 1 of lactation, reducing DCAD increased (P < 0.05) Cl concentration in serum (101.8 to 104.7 mEq/L). Collectively, negative DCAD increased Ca mobilization and decreased potential risk of urine tract infection without affecting litter performance.