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Agitation is common during the post-traumatic amnesia (PTA) period after traumatic brain injury (TBI), although our knowledge of what causes or predicts agitation is limited. The current study aimed to examine the association of agitation in PTA with the concurrent impairments in orientation and memory while controlling for covariates of agitation. Participants were 125 patients in PTA following moderate to extremely severe TBI recruited from an inpatient brain injury rehabilitation service who were assessed throughout PTA on the Agitated Behavior Scale (ABS) and the Westmead PTA Scale (WPTAS). Agitation was observed in 42.4% of participants (ABS score 21), with disinhibited behaviours (e.g., distractibility and impulsivity) most common. Multilevel modelling found daily ABS scores to be associated with daily scores on the WPTAS but in a non-linear pattern. Analysis of covariates found that shorter time post-admission, younger age, presence of infection and higher antipsychotic doses were associated with higher ABS scores. These results support a relationship between agitation and the concurrent cognitive impairment during PTA. While a causal link cannot yet be inferred, management strategies that can potentially interfere with cognition (e.g., sedating medications, environmental changes) should be used cautiously in case they exacerbate agitation.