This longitudinal, prospective study investigated associations between perceived COVID-19-related stress, coping strategies, and mental health status among adolescents during the first lockdown of the COVID-19 pandemic and one year after the lockdown in Switzerland within a large, national sample. A self-report on-line survey was completed by 553 adolescents (age-range 12–18 years in 2021) in the summers of 2020 and 2021, assessing symptoms of various mental health problems, perceived COVID-19-related stressors, and coping strategies. Overall, participants reported less COVID-19 related stress one year after the lockdown, though mental health status remained stable. ‘Challenges at home or with others’ were significantly associated with mental health problems in both genders, whereas ‘trouble getting medical care or mental health services ‘was associated with mental health problems in girls. Perceived stress and pre-existing psychiatric problem were significantly linked to all mental health outcomes at both time points. Parents’ poor relationships with partners during the lockdown was associated with increased anxiety symptoms in their children. Using cognitive restructuring to cope with stress was associated with less, while negative coping was associated with more anxiety, depression, and attention deficit hyperactivity disorder (ADHD) symptoms one year post lockdown. Girls appear to have been more affected by the pandemic than boys, with youths with pre-existing psychiatric problems especially vulnerable to its detrimental effects. Healthcare and school professionals should support to identify high-risk adolescents with negative and avoidant coping strategies and train youths to use positive coping strategies.