An experiment was conducted to examine effects of prepartum, postpartum, or continuous prepartum and postpartum supply of rumen-protected lysine (RPLys) and rumen-protected methionine (RPMet) on performance and blood metabolites of transition cows. The experiment consisted of a prepartum (3 wk), postpartum (3 wk), and carryover (10 wk) period. Eighty-eight prepartum cows (36 primiparous and 52 multiparous cows) were blocked by parity and expected calving date and assigned to 1 of 4 treatments arranged factorially. Treatments were a prepartum diet (12% crude protein on a dry matter basis) without (Pre-) or with supplemental RPLys (10 g of digestible Lys/cow per day) and RPMet (4 g of digestible Met/cow per day; Pre+) followed by postpartum diets (16% crude protein on a dry matter basis) without (Post-) or with supplemental RPLys (26 g of digestible Lys/cow per day) and RPMet (11 g of digestible Met/cow per day; Post+). Prepartum, only 2 treatments were applied, but postpartum cows received treatments of Pre-Post-, Pre-Post+, Pre+Post-, or Pre+Post+. During the prepartum period, treatment did not affect dry matter intake and body weight. During the postpartum period, milk protein content was greater (3.23 vs. 3.11%) for Post+ compared with Post- independent of prepartum treatment. However, dry matter intake, body weight, milk yield, and yields of milk components were not affected by Post+ versus Post-. No effects of prepartum treatment or interactions between pre- and postpartum treatments were observed on postpartum performance of cows. No effects of pre- and postpartum supplementation of RPLys and RPMet on performance during the carryover period were found except prepartum supplementation of RPLys and RPMet decreased somatic cell count (4.60 vs. 4.83; log transformed) compared with Pre- in the postpartum period and this effect continued during the carryover period [i.e., 4.42 and 4.55 (log transformed) for Pre+ and Pre-, respectively]. Prepartum supplementation of RPLys and RPMet increased or tended to increase plasma concentration of Lys, Met, and branched-chain AA compared with Pre- in prepartum cows. Cows on Post+ tended to have greater plasma Lys concentration compared with Post-, but plasma Met concentration was not affected. Health events of postpartum cows were not affected by treatments. In conclusion, we did not observe positive effects of supplementing with RPLys and RPMet on performance of prepartum and postpartum cows. However, prepartum supply of RPLys and RPMet may have potential to improve udder health and immune status of fresh cows.