Background: The impact of various lifestyles on psychological well-being (PWB) remains under-studied. We aimed to explore the cross-sectional association between daily screen use (television, tablet and mobile phone) and PWB within the SUN cohort. Methods: PWB was assessed using the 29-item Ryff scale (ranging from 29 to 174), and participants with scores >75th percentile were considered as having optimal PWB. Participants were categorized based on their self-reported weekly screen usage hours. Postestimation logistic regression models assessing the prevalence likelihood of not achieving optimal PWB were adjusted for sociodemographic, psychological, personality and lifestyles factors. Isotemporal substitution models explored the potential impact on PWB resulting from replacing 1 h/day of screen time with 1 h/day of exercise. Results: The study included 3051 participants (55.8% women, mean age 57.3 ± 11.1 years, mean Ryff's score: 139.1 ± 17.4 points). Daily screen use for ≥2 h was associated with a higher prevalence likelihood of not achieving an optimal PWB (Prevalence Ratio [PR]:1.09; 95% CI:1.01-1.18). Among PWB dimensions, screen use ≥2 h/day was linked to an increased likelihood of not achieving optimal scores in environmental mastery (PR:1.11; 95% CI:1.02-1.20), life purpose (PR:1.10; 95% CI:1.02-1.18), and personal growth (PR:1.09; 95% CI:1.01-1.18). Replacing 1 h of daily screens time with 1 h of exercise may lead to potential improvements in environmental mastery (Odds Ratio [OR]:0.87; 95% CI:0.76-0.99), purpose in life (OR:0.86; 95% CI: 0.76-0.98), personal growth (OR:0.84; 95% CI:0.73-0.96) and positive interpersonal relationships (OR:0.86; 95% CI:0.75-0.99). Conclusions: These findings highlight the importance of reducing screen use activities and increasing physical exercise for achieving optimal PWB.