OBJECTIVE: We hypothesized that greater screen use would be associated with greater psychological difficulties and that children with high levels of screen entertainment use and low levels of physical activity would have the most-negative psychological profiles. METHODS: Participants were 1013 children (age, mean ± SD: 10.95 ± 0.41 years), who self-reported average daily television hours and computer use and completed the Strengths and Difficulties Questionnaire. Sedentary time (minutes per day with <100 cpm) and moderate/vigorous physical activity (MVPA) (minutes with ≥2000 cpm) were measured by using accelerometers. Multivariate regression models examined the association between television viewing, computer use, sedentary time, and Strengths and Difficulties Questionnaire scores, with adjustment for MVPA, age, gender, level of deprivation, and pubertal status. RESULTS: Greater television and computer use were related to higher psychological difficulty scores after adjustment for MVPA, sedentary time, and confounders. However, sedentary time was inversely related to psychological difficulties after adjustment. Children who spent >2 hours per day watching television or using a computer were at increased risk of high levels of psychological difficulties (television, odds ratio [OR]: 1.61 [95% confidence interval [CI]: 1.20–2.15]; computer, OR: 1.59 [95% CI: 1.32–1.91]), and this risk increased if the children also failed to meet physical activity guidelines (television, OR: 1.70 [95% CI: 1.09–2.61]; computer, OR: 1.81 [95% CI: 1.02–3.20]). CONCLUSION: Both television viewing and computer use are important independent targets for intervention for optimal well-being for children, irrespective of levels of MVPA or overall sedentary time.