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The objective of this study was to estimate genetic parameters of predicted N use efficiency (PNUE) and N losses (PNL) as proxies of N use and loss for Holstein cows. Furthermore, we have assessed approximate genetic correlations between PNUE, PNL, and dairy production, health, longevity, and conformation traits. These traits are considered important in many countries and are currently evaluated by the International Bull Evaluation Service (Interbull). The values of PNUE and PNL were obtained by using the combined milk mid-infrared (MIR) spectrum, parity, and milk yield–based prediction equations on test-day MIR records with days in milk (DIM) between 5 and 50 d. After editing, the final data set comprised 46,163 records of 21,462 cows from 154 farms in 5 countries. Each trait was divided into primiparous and multiparous (including second to fifth parity) groups. Genetic parameters and breeding values were estimated by using a multitrait (2-trait, 2-parity classes) repeatability model. Herd-year-season of calving, DIM, age of calving, and parity were used as fixed effects. Random effects were defined as parity (within-parity permanent environment), nongenetic cow (across-parity permanent environment), additive genetic animal, and residual effects. The estimated heritability of PNUE and PNL in the first and later parity were 0.13, 0.12, 0.14, and 0.13, and the repeatability values were 0.49, 0.40, 0.55, and 0.43, respectively. The estimated approximate genetic correlations between PNUE and PNL were negative and high (from −0.89 to −0.53), whereas the phenotypic correlations were also negative but relatively low (from −0.45 to −0.11). At a level of reliability of more than 0.30 for all novel traits, a total of 504 bulls born after 1995 had also publishable Interbull multiple-trait across-country estimated breeding values (EBV). The approximate genetic correlations between PNUE and the other 30 traits of interest, estimated as corrected correlations between EBV of bulls, ranged from −0.46 (udder depth) to 0.47 (milk yield). Obtained results showed the complex genetic relationship between efficiency, production, and other traits: for instance, more efficient cows seem to give more milk, which is linked to deeper udders, but seem to have lower health, fertility, and longevity. Additionally, the approximate genetic correlations between PNL, lower values representing less loss of N, and the 30 other traits, were from −0.32 (angularity) to 0.57 (direct calving ease). Even if further research is needed, our results provided preliminary evidence that the PNUE and PNL traits used as proxies could be included in genetic improvement programs in Holstein cows and could help their management.