Abstract Background Suicidal ideation is a depression symptom which represents a key (cognitive) component of suicidality and plays an important role in suicide risk detection, intervention, and prevention. Despite existing research showing the importance of certain factors of depression symptoms and suicidal ideation, less is known about the interaction between the various risk and protective factors. The aim of the study was to examine whether living conditions characteristics and personal circumstances during the COVID-19 pandemic predicted the presence of depression symptoms and suicidal ideation among tertiary students and whether resilience and social support can mitigate the detrimental effects of difficult life circumstances. Method A large online cross-sectional study was conducted in March 2021 among 4,645 Slovenian tertiary students. Hierarchical multiple regression and hierarchical logistic regression methods were used to assess and compare the effect of life circumstances variables, as opposed to resilience and social support, on depression symptoms and suicidal ideation. Results Female gender, single relationship status, living alone, a higher degree of household conflict, having a history of mental illness and chronic disease diagnosis were significant predictors of depression scores. All but gender were also predictors of suicidal ideation. Household conflict and a history of mental illness were the factors showing the strongest effect in both cases. On the other hand, social support and, in particular, resilience proved to be strong protective factors against depression symptoms and suicidal ideation. After accounting for one’s resilience and social support, the explained variance in depression scores was more than doubled, while the harmful effect of household conflict and history of mental illness significantly decreased. Conclusions The findings stress the importance of one’s resilience and social support and explain why some people manage to maintain mental well-being despite finding themselves in difficult life circumstances, which was the case for many tertiary students during the COVID-19 pandemic. These insights may inform preventive efforts against developing suicidal ideation and may be used as support for the design and implementation of interventions for improving resilience and social support from childhood onward.