Background: Head injuries (HI) are a major threat to public health. Initial management should involve careful evaluation and neurological assessment. We aim to evaluate the predictive value of trans cranial duplex and jugular venous oxygen saturation in patients with deep-seated brain lesions after Head Trauma. Methods: A prospective study on 60 patients with deep-seated brain lesions after head trauma was conducted at the neurosurgical department and intensive care unit in Zagazig University Hospital. Trans cranial duplex and Jugular Venous Oxygen Saturation Monitoring were assessed in all patients. Results: The best cutoff of TCD (PI) at week 2 that can predict unfavorable outcomes among patients is ≥0.95 cm with area under curve 0.838 with 73.1% sensitivity and 60% specificity. The best cutoff of TCD (MFV) at week 2 that can predict unfavorable outcomes among patients is ≤39.5 cm/sec with area under curve 0.831 with 84.6% sensitivity and 60% specificity. The best cutoff of baseline SjVO2 that can predict unfavorable outcomes among patients is ≥73.5% with an area under curve 0.908 with 80.8% sensitivity and 60% specificity. Conclusion: There is a statistically significant relation between outcome and SjVO2 at ER admission and at each point of the follow-up period till the end of the second week where all those with favorable outcomes were discharged (higher levels significantly associated with unfavorable outcomes). There is a statistically significant relation between outcome and TCD (MFV) and TCD (PI) at ER admission, first and third week (lower TCD (MFV) and higher TCD (PI) were significantly associated with unfavorable outcome).