Powder metallurgy–hot isostatic pressing (PM-HIP) is a form of advanced manufacturing that offers the ability to produce near-net shape components that are otherwise not achievable via conventional forging or wrought manufacturing. Accessing the design space of PM-HIP is dependent upon the ability to achieve uniform or known properties in finalized components, which has resulted in a number of programs aimed at identifying properties achievable via PM-HIP manufacturing. One result of these programs has been the consistent observation of a variation in toughness observed for the low-alloy steel ASTM A508 Grades 3 and 4N. While observed, the degree of variability and the mechanism resulting in the variability have not yet been fully defined. Thus, a systematic approach to evaluate the variation observed in impact toughness in PM-HIP ASTM A508 Grade 4N was proposed to elucidate the responsible metallurgical mechanism. Four unique billets manufactured from two heats of powder with different particle size distributions (PSDs) were fabricated and tested for impact toughness and tensile properties. The degradation in impact toughness was confirmed to be location-specific where the near-can region of all billets had reduced impact toughness relative to the interior of each billet. The mechanism driving the location-specific property development was identified to be mobile oxygen that follows the thermal gradient that develops during the HIP cycle and leads to a redistribution of mobile oxygen where oxygen is concentrated ~1” inboard of the original canister/billet interface. Redistributed oxygen then forms stable oxides along coincident prior particle and prior austenite grain boundaries, effectively reducing the impact toughness. With the mechanism now addressed, necessary actions can be taken to mitigate the effect of the oxygen redistribution, allowing for use in PM-HIP A508 Grade 4N in commercial industry.