Complaints of fatigue following acquired brain injury (ABI) are often associated with depression. However, the nature of this relationship is unclear; furthermore, research among young people with ABI is limited. The objective of this cross-sectional study was (1) to investigate levels of depression in young outpatients with ABI (15–30 years old) and (2) to determine how different dimensions of fatigue relate to depression. Five dimensions of fatigue were assessed with the Multidimensional Fatigue Inventory (MFI-20), and depression was assessed with the Major Depression Inventory (MDI). Mann–Whitney U-tests and multiple regression analyses were conducted. The ABI group (n = 105), on average 23.7 years old (SD = 4.2) and 31 months post-injury (SD = 61), had elevated levels of fatigue and depression compared to a convenience sample of 160 healthy controls, all p’s < .001. In multivariate analyses, the predominantly mental dimensions of fatigue, General Fatigue, Mental Fatigue, and Reduced Motivation, were independently associated with MDI, all p’s < .01, while the physical dimensions, Physical Fatigue and Reduced Activity, were not. Distinctions within the concept of fatigue may be important in relation to depression, and future research could benefit from adopting a multidimensional approach in the development of more targeted and effective treatments of fatigue and depression following ABI.