Background: Parents who lose a child are at increased risk of impaired mental health, which may negatively affect their work ability. The aims of this study were to examine the risk for reduced labor market affiliation in parents who lost a child with cancer compared to a matched parent cohort, and factors associated with the bereaved parents’ labor market affiliation. Methods: We conducted a nationwide population-based cohort study using Danish registry data. We followed bereaved parents (n = 1609) whose child died with cancer at age less than 30 during 1992–2020, and a matched, population-based sample of parents (n = 15,188) of children with no history of childhood cancer. Cox proportional hazard models and fractional logit models were performed separately for mothers and fathers. Results: Cancer-bereaved mothers had an overall increased risk of long-term sick leave (hazard ratio [HR] = 1.62; 95% confidence interval [CI]: 1.48–1.77), unemployment (HR = 1.53; CI: 1.37–1.70), and lower odds of working in the first 2 years following the loss (odds ratio [OR] = 0.44; CI: 0.39–0.49), while bereaved fathers had lower odds of working (OR = 0.65; CI: 0.53–0.79), and increased risk of permanently reduced work ability (HR = 1.29; 95% CI: 1.01–1.66), compared to the matched cohort of parents of cancer-free children. Younger parental age, lower education, and being a single parent were identified as the main determinants of the bereaved parents’ reduced labor market affiliation. Conclusions: Cancer-bereaved parents are at increased risk of reduced labor market affiliation, compared with a matched, population-based sample of parents. Certain groups of bereaved parents may be at particularly high risk, and targeted bereavement interventions are warranted.