The COVID-19 pandemic has had a significant influence on the lives of people around the world and could be a risk factor for mental health diseases. This study aimed to explore the psychological impact of the COVID-19 pandemic by identifying patterns related to post-traumatic symptoms by considering personality and defensive styles. Specifically, it was hypothesized that neuroticism was negatively associated with impact of event, as opposed to extraversion, agreeableness, conscientiousness, and openness traits. The mediation role of mature, neurotic, and immature defenses in these relationships was also investigated. This study involved 557 Italian individuals (71.3% women, 28.7% men; Mage = 34.65, SD = 12.05), who completed an online survey including the Impact of Event Scale-Revised, Forty Item Defense Style Questionnaire (DSQ-40) and Ten Item Personality Inventory. Results showed a nonsignificant effect for extraversion and openness on impact of event. The negative influence of neuroticism was instead confirmed in a partial parallel mediation involving significant effects from immature and neurotic defenses in the indirect path. Finally, agreeableness and conscientiousness delineated two protective pathways regarding impact of event, determining two total parallel mediation models in which both these personality traits were negatively associated with immature defensive styles, and conscientiousness was also positively related to mature defenses. These findings provide an exploration post-traumatic symptom patterns during the COVID-19 pandemic, involving the big five personality traits and defense mechanisms. These results may be useful for developing interventions, treatments, and prevention activities.