In early lactation, dairy cows typically have a negative energy balance which has been related to metabolic disorders, compromised health and fertility, and reduced productive lifespan. Assessment of the energy balance, however, is not easy on the farm. Our aims were to investigate the milk metabolic profiles of dairy cows in early lactation, and to obtain models to estimate energy balance from milk metabolomics data and milk production traits. Milk samples were collected in week 2 and 7 after calving from 31 dairy cows. For each cow, the energy balance was calculated from energy intake, milk production traits and body weight. A total of 52 milk metabolites were detected using LC-QQQ-MS. Data from different lactation weeks was analysed by partial least squares analysis, the top 15 most relevant variables from the metabolomics data related to energy balance were used to develop reduced linear models to estimate energy balance by forward selection regression. Milk fat yield, glycine, choline and carnitine were important variables to estimate energy balance (adjusted R2: 0.53 to 0.87, depending on the model). The relationship of these milk metabolites with energy balance is proposed to be related to their roles in cell renewal.