Background There is a growing body of literature that recognizes the significant impact of COVID-19 on mental health. Over the past two years, studies have provided important information about individuals’ well-being in different countries. Nonetheless, most of the existing literature has focused on the first months of the pandemic. Aims This study explores the longitudinal course of various mental health factors and coping behaviors during the pandemic of coronavirus in Greece across three assessment waves within six month-interval. Methods The participants of the study were 92 and completed the survey online. Symptoms of adjustment disorder, depression, anxiety and poor well-being were examined as well as resilience and pandemic-related coping behaviors. Gender differences were also investigated. Results Overall, the findings indicated that the participants’ mental health was most affected during the second assessment wave (April to June 2021) and less during the third assessment wave (October 2021). Some shifts to coping strategies were also noticed. Conclusions The implications of the results are discussed in light of designing well-structured future policies.