Despair can occur following stressful events such as death, economic hardship, loss of status or perceived purpose, the end of a relationship, and more.

It can also be influenced by past experiences (e.g., childhood trauma) and environmental factors (e.g., changes caused by new technologies, shifts in societal culture, or the tone of media narratives), leading to negative thoughts and the solidification of painful beliefs ("I'm broken" or "I'm useless.") In turn, these beliefs may result in deeply negative emotions like despair and dangerous behaviors such as withdrawal from others, substance use, or life-threatening actions.

We often experience despair alone, even when the event that caused our pain also affected others at the same time and in the same way. This is evident, for instance, when a couple suffers a terrible loss, like the loss of a child, and drifts apart, each feeling despair in isolation. In such cases, remembering that we are not alone in our pain may help soften despair by easing the loneliness that comes with it.

Despair is difficult to distinguish from other emotions, like hopelessness and resignation. First, despair differs from hopelessness in terms of scope. We may lose hope about a particular aspect of life, like love or work, while feeling hopeful in other things. In addition, despair differs from resignation in intensity. While we may resign to accepting a situation we find bearable, like an "ok" relationship or job, a person in despair cannot bear their current situation.