Objectives: Recent research has suggested that psychological symptoms following mild traumatic brain injury (mTBI) are present much earlier than expected in the development of post-concussion syndrome (PCS). Furthermore, in the acute stage post-trauma (i.e. within 14 days) Meares et al. found the variables most strongly related to a diagnosis of PCS were the presence of a previous affective or anxiety disorder and female sex, rather than the occurrence of the mTBI itself. The question of the extent to which these factors contribute to persistent PCS is central. The aim of the current study was to examine predictors of PCS at two time points, within the acute stage and in the chronic phase (i.e. 3 months) post-trauma. The relationship between preinjury psychiatric disorder, demographic factors, injury-related characteristics, neuropsychological and psychological variables and PCS was investigated. Method: Consecutive trauma admissions to a Level 1 trauma hospital were prospectively enrolled if they had suffered a traumatic injury. The final sample comprised 62 mTBI and 58 non-brain injured trauma controls who were assessed at both time points, a mean 4.88 days (SD=2.72) and a mean 106.23 days (SD=14.85) post-trauma. On both occasions participants were administered a PCS checklist and neuropsychological and psychological measures. Diagnosis of PCS was based on the presence and frequency of three or more PCS symptom complaints from the International Classification of Diseases PCS diagnostic criteria. Mixed-effects logistic regression was used to test associations between subject characteristics and the effect of time. Multiple imputation was used to handle missing data at the subject level. Results: At both times a diagnosis of PCS was not specific to mTBI (acute stage: mTBI 40.3%, controls 50.0%; chronic phase: mTBI 46.8%, control 48.3%). The strongest predictor of PCS in both the acute and chronic phase was female sex (OR: 2.77, 95% CI, 1.01–7.55). Individuals with premorbid anxiety or affective disorder were 2.72- times more likely to have PCS at both times than those without psychological histories (95% CI, 1.04–7.17). Pain and post-traumatic stress disorder (PTSD) were each individually significant predictors of PCS ~3 months post-trauma. At this time participants were 3.6-times more likely to have PCS if they were experiencing both pain and PTSD (95% CI, 1.21–10.72). Conclusions: Female sex and premorbid anxiety and affective disorder were stable predictors of PCS, suggesting that PCS may be validly diagnosed in the acute stage post-trauma. The diagnosis of PCS in the acute stage, rather than later in the chronic phase, followed by early intervention may reduce the development of psychological disorders in these vulnerable individuals.