Purpose/Objective: This study explored associations of psychological inflexibility with depressive symptoms, anxiety, and stress in individuals living with spinal cord injuries (SCI). Research Method/ Design: The study used a cross-sectional design involving data of self-reported questionnaires collected from 92 adults with SCI in the United States. These questionnaires included measures of depressive symptoms, anxiety, and stress as the dependent variables and measures of potential independent variables, including demographic and SCI-related variables, psychological inflexibility, pain interference, independence, and ability to participate in and satisfaction with social roles and activities. Multivariable linear regression analyses were conducted. Stepwise method, forward selection, and backward elimination procedures, supplemented with the best subsets method, were used to obtain the most parsimonious set of independent variables for each of the depressive symptoms, anxiety, and stress scores. Results: The current study showed that psychological inflexibility, employment status, and time since the injury were variables significantly associated with depressive symptoms, and that psychological inflexibility and ethnicity/race were variables significantly associated with anxiety. Psychological inflexibility was the only variable significantly associated with stress. Conclusions: Findings of the present study suggest the importance of psychological flexibility in depressive symptoms, anxiety, and stress in individuals with SCI by showing significant associations among these variables. This exploratory study informs the need for further studies involving interventions that aim to foster greater psychological flexibility, which may decrease mental health problems in individuals with SCI.