Living in a nursing home can provide essential support for older adults, yet may also give rise to existential challenges that may contribute to the elevated prevalence of depressive symptoms among nursing home residents (NHRs). Existing research largely emphasizes bio-psycho-social risk factors, paying comparatively limited attention to existential concerns relating to depressive symptoms – and whether they represent meaningful targets for mental health interventions in nursing homes. This study examined the longitudinal associations between two existential concerns – meaning in life (MIL) and existential loneliness (EL) – and depressive symptoms in 243 residents from 22 Belgian nursing homes assessed annually over three years. Random intercept cross-lagged panel models were used to disentangle between-person and within-person effects. At the between-person level, residents with higher MIL and lower EL reported fewer depressive symptoms. At the within-person level, associations were more complex and reversed: depending on the model, increases in EL predicted fewer depressive symptoms over time, and higher depressive symptoms predicted subsequent increases in MIL. These findings diverged from conclusions based on classical cross-lagged models, indicating that existential concerns relate to depressive symptoms among NHRs differently depending on analysis level. While the between-person findings suggest the existence of a vulnerable subgroup of residents with persistently elevated existential concerns and concurrent depressive symptoms, it remains unclear whether changes in existential concerns will consistently translate into reductions in depressive symptoms within individuals over time. This highlights the need for further research on within-person existential dynamics, potentially on shorter timescales, to inform evidence-based intervention development in nursing homes.