The objective was to study associations among indicators of feed efficiency and selected milk metabolites during early lactation, and in response to experimental feed restriction (FR) for the discovery of non-invasive proxies. 28 cows divergent in phenotypic residual feed intake (RFI; positive or negative) were selected, each RFI group composed of 14 Holstein and 14 Montbéliarde cows. Energy balance (EB) and conversion efficiency (ECE; NEL secreted/intake) were calculated. Early lactation RFI (RFIearlylact) was measured during the first 10 wks of lactation. Starting at 87±9 DIM, cows underwent four 4-day periods of FR to meet 50% of individual energy requirements (FR1-FR4). Mid-lactation RFI (RFImidlact) was measured during 5 wks following FR4, as described (doi.org/10.1016/j.anscip.2022.07.181). Milk isocitrate, glucose, glucose-6-phosphate, malate, glutamate and free amino groups (NH2-groups) were measured on wk 1, 2, 3, 4, 6 and 8, and daily during FR1 only. Data was analysed using mixed models with repeated measures, and spearman correlations. RFIearlylact ranged from -0.44 to -2.39 for negative RFIearlylact (i.e. more efficient), and from 0.42 to 2.34 kg DMI/d for positive RFIearlylact groups. Early lactation ECE was higher, whereas EB, plasma glucose, milk glucose, NH2-groups and glutamate were lower for the negative RFIearlylact group. Average early lactation milk glutamate and NH2-groups from wk1 to 8 were correlated with RFIearlylact (r= 0.44 and 0.41), but not with RFImidlact. No milk metabolite RFI group differences were observed during FR1. Weekly EB was positively correlated with milk glucose and malate (r=0.30 and 0.32), and negatively correlated with milk isocitrate and NH2-groups (r=-0.25 and -0.17), and the inverse correlations were observed for ECE. RFIearlylact associations with plasma glucose, milk glucose, NH2-groups and glutamate during early lactation may reflect in prioritization of nutrients towards milk secretion in more efficient cows. Conversely, these effects may be due to the lower EB experienced by cows with negative RFIearlylact.