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The clinical presentation of Parkinson’s disease (PD) is often dominated by depressive symptoms, which can significantly impact the patients’ quality of life (QoL). However, it is not clear how these depressive symptoms are interconnected, or if some symptoms are more influential in affecting QoL. In the Cohort of Patients with Parkinson’s Disease in Spain (COPPADIS) study, 686 patients with PD were analyzed using network analyses. The patients completed the Beck Depression Inventory II (BDI-II) and provided their overall QoL (EUROHIS-QOL) at the beginning of the study. The study used centrality measures such as Expected Influence and Bridge Expected Influence to identify depressive symptoms that had the greatest impact on overall QoL. The results of exploratory network analyses indicate that the BDI-II items related to loss of energy, past failure, and tiredness or fatigue have the greatest impact on overall QoL as measured by the EUROHIS-QOL 8-item index. The loss of energy and tiredness or fatigue BDI-II items are also strongly associated with a number of different EUROHIS-QOL items, according to Bridge Expected Influences. For individuals suffering from PD, network analysis can aid in identifying significant non-motor symptoms that impact their QoL, thus paving the way for potential improvements.