Multiparous dairy cattle in the Northeastern US were enrolled in a prospective cohort study with the objective of quantifying circulating AA and plasma metabolites during the transition period and creating a Metabolite Health Index (MHI). Farms were enrolled as either experiment (EXP; n = 7 farms): postpartum (POST) rumen-protected Met supplementation of > 11.25 g/d (Smartamine M; Adisseo, Antony, France) or control (CON; n = 5 farms): POST rumen-protected Met supplementation of ≤ 11.25 g/d. Prepartum (265 to 280 DCC; n = 168) and POST (5 to 17 DIM; n = 179) cows were sampled within each farm. All cows sampled were considered eligible for milk analysis whereas only POST cows were eligible for the metabolite analysis. Data were analyzed in SAS with PROC MIXED and repeated measures analysis was conducted for measures with multiple time points. Multivariable models were created using PROC MIXED to predict wk 4 milk (WK4M) and energy-corrected milk (ECM) at first test day, with MHI as the main risk factor of interest. Plasma urea concentrations were lower for EXP than CON cows (8.83 vs. 10.61 mg/dL; P < 0.01). Yield of ECM was higher in EXP through the 4th test day (49.2 vs. 45.4 kg/d; P < 0.01). There was a treatment × parity interaction for WK4M such that there was no difference between treatments for 2nd lactation cows (P = 0.31) whereas ≥ 3rd lactation EXP cows had greater WK4M than CON ≥ 3rd lactation cows (51.9 vs. 44.0 kg; P = 0.01). A MHI (range: −10.50 to 6.57) was created based on postpartum plasma bilirubin, cholesterol, and albumin concentrations sampled between 5 and 17 DIM. The EXP cows had a greater index than CON cows (0.25 vs. −0.42; P = 0.02) indicating better postpartum health status. A 1-unit increase in MHI resulted in a +0.86 kg WK4M response (P < 0.01). Similarly, a 1-unit increase in MHI resulted in a +1.32 kg ECM response (P < 0.01). Supplementation of Met was shown to improve MHI, ECM, and WK4M for ≥ 3rd lactation cows. A greater MHI was associated with greater WK4M and ECM, indicating healthy and more productive cows.