Objective Severe grief symptoms in family caregivers during end‐of‐life cancer trajectories are associated with complicated grief and depression after the loss. Nevertheless, severe grief symptoms during end‐of‐life caregiving in caregivers to cancer patients have been scarcely studied. We aimed to explore associations between severe preloss grief symptoms in caregivers and modifiable factors such as depressive symptoms, caregiver burden, preparedness for death, and end‐of‐life communication. Methods We conducted a population‐based prospective study of caregivers to 9512 patients registered with drug reimbursement due to terminal illness, and 3635 caregivers responded. Of these, 2865 caregivers to cancer patients completed a preloss grief scale (Prolonged Grief 13, preloss version). Associations with factors measured during end‐of‐life caregiving were analyzed using logistic regression. Results Severe preloss grief symptoms were reported by 432 caregivers (15.2%). These symptoms were associated with depressive symptoms (adjusted odds ratio [OR] = 12.4; 95% CI, 9.5‐16.3), high caregiver burden (adjusted OR = 8.3; 95% CI, 6.3‐11.1), low preparedness for death (adjusted OR = 3.3; 95% CI, 2.5‐4.4), low level of communication about dying (adjusted OR = 3.2; 95% CI, 2.2‐4.4), and “too much” prognostic information (adjusted OR = 2.8; 95%, 1.7‐4.6). Conclusions Severe preloss grief symptoms were significantly associated with distress, low preparedness, and little communication during caregiving. Thus, severe preloss grief symptoms may be a key indicator for complications in caregivers of cancer patients in an end‐of‐life trajectory. Targeted interventions are needed to support family caregivers with severe preloss grief symptoms. Development of preloss grief assessment tools and interventions should be a priority target in future research.