Background: Patients with serious illness frequently report (temporary) wishes to hasten death. Even until the end-of-life, many patients also harbor a will to live. Although both phenomena are negatively correlated according to some studies, they can also co-exist. Knowledge about the complex relationship between the seemingly opposing wish to hasten death and will to live is limited, but crucial for delivering adequate care and understanding potential requests for assisted dying. Aim: To study the correlation of and explore the relationship between wish to hasten death and will to live over 6 weeks. Design: Observatory, prospective cohort study following a mixed methods design. Analysis of quantitative (Schedules of Attitudes Toward Hastened Death, a visual numerical scale and (additional) validated questionnaires) and qualitative (semi-structured interviews) data with illustrative case descriptions. Setting/participants: Patients receiving palliative care with heterogenous underlying diseases from various care settings, before and after an open conversation on a possible desire to die. Results: In n = 85 patients, wish to hasten death and will to live were strongly negatively correlated at three time points (baseline: r(65) = −0.647, p ⩽ 0.001; after 1 week: r(55) = −0.457, p ⩽ 0.001 and after 4–6 weeks: r(43) = −0.727, p ⩽ 0.001). However, visual assessment of scatterplots revealed a small, but substantial number of outliers. When focusing on these outlier patients, they showed clinically relevant changes between baseline and 6 weeks with the wish to hasten death changing in n = 9 (15% of n = 60) and the will to live changing in n = 11 (18.6% of n = 59). Interview data of three outlier cases illustrates unusual trajectories and possible factors which may influence them. Conclusions: As they can co-exist in different possible combinations, a high wish to hasten death does not necessarily imply a low will to live and vice versa. Patients receiving palliative care can hold such seemingly opposing positions in mind as a form of coping when confronted with an existential threat of serious illness. Therefore, health professionals are encouraged to proactively engage patients in conversation about both phenomena.