This study examines whether character strengths predict resilience (operationalized as stable or higher mental health and subjective well-being despite an adverse event) over a period of approximately 1 month during the COVID-19 pandemic lockdown in Spain. Using a longitudinal design, participants (N = 348 adults) completed online measures of sociodemographic data, information regarding their situation in relation to the COVID-19, character strengths, general mental health, life satisfaction, positive affect and negative affect. All variables were measured at Time 1 and Time 2, except for sociodemographic and most COVID-related information (Time 1 only). Time 1 data collection was conducted between March 21, 2020 and April 2, 2020, i.e., approximately the second week of lockdown in Spain. Time 2 data collection was conducted between April 24, 2020 and May 18, 2020, after the Spanish government announced its intention to progressively release the lockdown. A principal component analysis of character strengths was conducted. Five character strength factors were extracted: fortitude, goodness, intellectual, interpersonal, and restraint. Factor structures at Times 1 and 2 were highly consistent. All character strength factors at Time 1 correlated positively with life satisfaction and positive affect, and negatively with negative affect and mental health at T2 (higher scores in the mental health measure indicate poorer mental health). Fortitude strengths showed the highest correlations. We conducted a series of regression analyses with strength factors at Time 1 as predictors, and mental health, life satisfaction, and positive and negative affect as dependent variables, controlling for their baseline levels. To test the directionality of the relationship between strengths and the dependent variables, all analyses were reversed. All character strength factors predicted an increase in mental health. They also predicted positive affect, with the exception of strengths of restraint. Fortitude, intellectual, and interpersonal strengths predicted an increase in life satisfaction. Finally, fortitude strengths, interpersonal strengths, and strengths of restraint, predicted a decrease in negative affect. None of the reversed analyses yielded significant effects. Limitations, implications, and possible character strengths-based interventions aimed at promoting mental health in the COVID-19 pandemic are discussed.