The COVID-19 pandemic brought about unprecedented changes and challenges to workers’ work and home lives. The current study integrated insights from theories (e.g., the job demands-resources model, COR theory) and literature to investigate the contributors (e.g., job demands, job resources, job involvement, work engagement) to workers’ experiences of ill-being and well-being (i.e., work-life conflict, strain, burnout, job satisfaction). We tested our hypotheses with data from 693 full-time US and Canadian workers from MTurk, a sample of university faculty, a snowball sample, and a sample of veterinarians. We found that workers with greater job demands experienced greater ill-being (e.g., work-life conflict), and workers with greater job resources experienced greater well-being (e.g., job satisfaction). However, different types of job resources predicted different outcomes (e.g., general job resources predicted lower strain, but stimulating and supportive job resources did not). Further, we did not find evidence that job resources protected workers against job demands and strain or work-life conflict. Our results also suggest that stimulating job resources may have negative outcomes for workers, as they predicted exhaustion, through greater work engagement and work-life conflict. In addition, greater work engagement predicted both positive (i.e., job satisfaction) and negative outcomes for workers (i.e., work-life conflict, strain), supporting the notion that work engagement may be a double-edged sword. Finally, exploratory analyses revealed the job demands and job resources that are most salient and pertinent during the pandemic for workers. Implications for theory and practice are discussed.