Background: Although the Coronavirus Disease 2019 (COVID-19) has greatly impacted individuals' mental health and quality of life, network analysis studies of associations between symptoms of common syndromes during the pandemic are lacking, particularly among Macau residents. This study investigated the network structure of insomnia, anxiety, and depression and explored their associations with quality of life in this population. Method: This online survey was conducted in Macau between August 18 and November 9, 2020. Insomnia, anxiety, depressive symptoms, and quality of life were assessed with the Insomnia Severity Index, Generalized Anxiety Disorder Scale, Patient Health Questionnaire, and World Health Organization Quality of Life-brief version, respectively. Analyses were performed to identify central symptoms and bridge symptoms of this network and their links to quality of life. Results: 975 participants enrolled in this survey. The prevalence of depressive, anxiety and insomnia symptoms were 38.5% (95% confidence interval (CI): 35.5%–41.5%), 28.8% (95%CI: 26.0%–31.7%), and 27.6% (95% CI: 24.8%–30.4%), respectively. “Sleep maintenance” had the highest expected influence centrality, followed by “Trouble relaxing”, “Interference with daytime functioning”, “Irritability”, and “Fatigue”. Five bridge symptoms were identified: “Sleep problems”, “Restlessness”, “Irritability”, “Severity of sleep onset”, and “Motor activity”. The insomnia symptom, “Sleep dissatisfaction”, had the strongest direct relation to quality of life. Conclusion: Insomnia symptoms played a critical role in the distress symptom network regarding node and bridge centrality as well as associations with quality of life among Macau residents. Close attention to these symptoms may be critical to reducing risk and preventing exacerbations in common forms of distress in this population.