Background: Critically ill patients are at high risk of developing mental and psychological disorders during admission in critical care units, often experiencing symptoms like anxiety, depression, and stress. The environment of critical units can be particularly distressing, especially during a first admission. Anxiety, depression, and stress significantly impact patients' quality of life and can hinder physical activities and social interactions. These psychological challenges can prolong recovery and increase the burden on healthcare systems. Family caregivers also face significant psychological distress, often leading to stress, anxiety, and depression. In Oman, no studies have explored these emotional distresses and related factors among critically ill patients and their caregivers. Purpose: This study was conducted to measure the level of perceived anxiety, depression and stress in both patients and their caregivers within critical care units and to identify the key risk and protective factors associated with the development of these mental health conditions. Methods: A descriptive cross-sectional, exploratory design was used to identify demographic and medical variables, and psychological distress among critically ill patients and their family caregiver. A sample of 440 of participants from patients and family caregivers were recruited from selected governmental hospitals in Muscat in Oman, using convenience sampling technique. Data was collected using the Depression Anxiety Stress Scale to measure psychological distress of (depression, anxiety and stress), Acute Physiology and Chronic Health Evaluation (APACHE) II score to measure disease severity based on current physiologic measurements. Linear multiple regression analyses were used to identify factors associated with patient’s and caregiver’s psychological distress. Result: The study found that anxiety prevalence among patients was mild (10.0%), moderate (7.7%), severe (1.4%), and extremely severe (5.9%), whereas caregivers exhibited higher rates of mild (22.3%), moderate (14.5%), severe (7.7%), and extremely severe (5%). Patients showed higher levels of moderate (23.2%) and extremely severe (5%) depression. For stress, patients had 8.2% severe and 1.8% extremely severe levels. Using a linear regression model, the study identified that higher patient depression, stress, and diastolic blood pressure increased anxiety, while cardiac-related admissions and being in a surgical HD department reduced it. Depression was significantly influenced by patient stress, anxiety, bicarbonate levels, and caregiver stress. Stress levels correlated positively with patient depression and anxiety but negatively with bicarbonate levels. For caregivers, higher patient anxiety, caregiver depression, caregiver stress, and longer travel distances increased anxiety, whereas financial support, caregiving for another critically ill family member, and moderate income lowered it. Caregiver depression was driven by caregiver anxiety, stress, duration of care, and low income. Stress in caregivers was heightened by caregiver depression, anxiety, and financial support, but reduced by solo caregiving, longer travel distances, and having a home assistant. Conclusion: This study provides essential insights into the prevalence and risk factors of anxiety, depression, and stress among patients admitted to critical care units and their family caregivers in Oman. The findings highlight the significant psychological impact on both patients and caregivers, underscoring the need for interventions to improve their mental well-being. Implementing supportive measures can enhance the quality of life for caregivers and contribute to better outcomes for critically ill patients.