Severe traumatic brain injury (TBI) is a multifactorial injury process involving respiratory, cardiovascular and immune functions in addition to the brain. Thus, live animal models are needed to study the molecular, cellular and systemic mechanisms of TBI. The ethical use of laboratory animals requires that the benefits of approaches be carefully weighed against potential harm to animals. Welfare assessments adapted to severe TBI research are lacking. Here, we introduce a scoresheet to describe and monitor potential distress in animals, which includes general welfare (body weight, general appearance and spontaneous behaviour) and TBI-specific indices (respiratory function, pain, locomotor impairment, wound healing). Implementation of this scoresheet in Sprague–Dawley rats subjected to severe lateral fluid percussion TBI revealed a period of suffering limited to four days, followed by a recovery to normal welfare scores within 10–15 days, with females showing a worse impact than males. The scores indicate that animal suffering in this model is transitory compared with TBI consequences in humans. The scoresheet allows for the implementation of refinement measures including (1) analgesia during the initial period following TBI and (2) humane endpoints set (30% weight loss, score ≥90 and/or respiratory problems). This animal scoresheet tailored to TBI research provides a basis for further refinement of animal research paradigms aimed at understanding or treating the sequelae of severe TBI.