The primary lesion arising from the initial insult after traumatic brain injury (TBI) triggers a cascade of secondary tissue damage, which may also progress to connected brain areas in the chronic phase. The aim of this study was, therefore, to investigate variations in the susceptibility distribution related to these secondary tissue changes in a rat model after severe lateral fluid percussion injury. We compared quantitative susceptibility mapping (QSM) and R * measurements with histological analyses in white and grey matter areas outside the primary lesion but connected to the lesion site. We demonstrate that susceptibility variations in white and grey matter areas could be attributed to reduction in myelin, accumulation of iron and calcium, and gliosis. QSM showed quantitative changes attributed to secondary damage in areas located rostral to the lesion site that appeared normal in R * maps. However, combination of QSM and R * was informative in disentangling the underlying tissue changes such as iron accumulation, demyelination, or calcifications. Therefore, combining QSM with R * measurement can provide a more detailed assessment of tissue changes and may pave the way for improved diagnosis of TBI, and several other complex neurodegenerative diseases.© 2020 John Wiley & Sons, Ltd.