Objectives: The current study examined whether hope and mindfulness were associated with changes in two maladjustment measures, internalizing and externalizing behaviors, during the COVID-19 pandemic and tested sense of coherence as a mediator. The salutogenic theory of health, which posits that sense of coherence is central to individuals’ well-being in stressful situations and that individuals derive their sense of coherence from their generalized resistance resources (GRRs), was used to guide the analyses. Methods: On two occasions separated by about 6 months, 253 Hong Kong college students (mean age = 21.0 years at time 1; 86% of them were women) filled in online questionnaires during the COVID-19 outbreaks. Path analysis was conducted to examine the interrelationships among hope and mindfulness, sense of coherence, and internalizing and externalizing behaviors. Results: Results indicated that hope and mindfulness at time 1 were associated with internalizing and externalizing behaviors at time 2, even after controlling for confounding variables and prior levels of internalizing and externalizing behaviors. Moreover, sense of coherence at time 1 significantly mediated these associations. Conclusions: Findings pointed to the potential roles of hope, mindfulness, and sense of coherence in understanding Chinese college students’ adjustment during the COVID-19 pandemic. Future research is needed to test whether sense of coherence and behavioral adjustment can be promoted through hope- and mindfulness-based intervention programs. Future research is also needed to examine the interrelationships among health-promoting assets, sense of coherence, and individual adjustment in samples of diverse cultural backgrounds. Copyright © 2022 The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.