Body-centered cubic refractory metals, as a class of critical structural materials, are often restricted by poor low-temperature toughness, which is a common, undesirable phenomenon that continues to be the focus of intense research. Historically, rhenium (Re) has been considered the most promising alloying element in improving ductility and reducing the ductile-to-brittle transition (DBT) temperature of group-VI metals, known as the “Re effect”. However, whether this is indeed possible remains uncertain so far. Here, in the modelled W-xRe (x = 0, 3, 5, 10 wt.%) alloys, we reveal that only in a limited temperature range of 50 °C∼200 °C does the Re softening occur, imparting a positive but small effect on fracture toughness. At higher temperatures (>300 °C), the dynamic interactions between Re solutes and dislocations produce profuse jogs and sessile loops that strongly hinder dislocation motion and cause hardening. The resultant difficulty in plastic flow significantly degrades the high-temperature (>300 °C) toughness of W-Re alloys, leading to an undesirable increase of the DBT temperature, which shifts higher with increasing Re content. Our discovery of the solution softening-to-hardening transition, including its dislocation mechanism, clarifies the intrinsic effect of Re on the toughness of recrystallized W alloy, providing essential knowledge for the compositional design of refractory alloys in general.