While clinical surveys have frequently reported that patients with traumatic brain injuries (TBIs) and comorbidities experience faster healing, the underlying mechanisms have been investigated but remain unclear. As a comprehensive comparison and analysis of the metabolic characteristics of these two pathologies have not been undertaken, we developed a rat model of fracture and TBI and collected serum samples for metabolomic analysis using ultra‐high performance liquid chromatography–quadrupole time‐of‐flight MS (UHPLC–Q‐TOF/MS). In total, we identified 40 differential metabolites and uncovered related pathways and potential mechanisms, including aminoacyl‐transfer RNA biosynthesis; differential amino acids such as leucine, cholylhistidine, aspartyl‐lysine; and related lipid metabolism, and discussed their impacts on bone formation in detail. This study highlights that the UHPLC–Q‐TOF/MS–based metabolomics approach offers a better understanding of the metabolic links between TBI and accelerated bone recovery.