First principles calculation is performed to comparatively investigate the effects of Cu and Fe on energetics, cohesion properties, elastic properties, and fracture toughness of the ∑5(310)[001] grain boundary (GB) in body-centered cubic (BCC) W. It shows that both Cu and Fe have a tendency to segregate towards GB of BCC W and increase stability of GB with a lower GB energy. Calculations also indicate that Cu and Fe have a significant effect on decreasing the cohesion and increasing the brittleness of BCC W, which should be fundamentally attributed to lower bond energies of W–Cu and W–Fe bonds than the W–W bonds. The obtained results are interpreted and understood by bond energies and electronic structures, are consistent with existing experimental and theoretical observations, and would clarify the controversy about the effects of Cu and Fe on cohesion properties and brittleness of BCC W in the literature.