Two-dimensional nuclear magnetic resonance (2D NMR) is increasingly explored as a tool for metabolomics because of its superior resolution compared to one-dimensional NMR (1D NMR). However, 2D NMR is characterized by longer acquisition times, which makes it less suitable for high-throughput studies. In this Article, we evaluated two methods for the acceleration of nD NMR, ultrafast (UF) and nonuniform sampling (NUS), in the context of metabolomics. To this end, model samples mimicking the metabolic profile variations in serum from subjects affected by colorectal cancer and controls were analyzed by 1D (1)H NMR along with conventional and accelerated DQF-COSY and HSQC. A statistical analysis (OPLS-DA) yielded similar results for the group separation with all techniques, but biomarker identification from 2D spectra was substantially enhanced, both in terms of number of molecules and easiness of assignment. Most interestingly, fast 2D NMR techniques lead to similar results as conventional 2D NMR, opening the way for high-throughput metabolomics studies using 2D NMR.