Introduction: Although depression is commonly accompanied by cognitive deficits, the underlying mechanism remains unclear. One possibility is that such deficits are related to abnormal brain network connections. The purpose of this study was thus to investigate changes in brain functional connectivity (FC) in depression and its relationship with cognitive deficits., Methods: We enrolled 37 first-episode MDD patients and 53 matched healthy controls (HC). All participants completed clinical and neurocognitive assessments and underwent resting-state functional MRI. Seed-based analysis was used to define the dorsolateral prefrontal cortex (DLPFC) and FC analysis was then performed. We used bias correlation to analyze the correlation between FC and clinical and neurocognitive scores., Results: MDD patients showed increased FC of the right DLPFC with the left inferior temporal gyrus, left cuneus, right inferior frontal gyrus, right anterior cingulate cortex, left BA39, right angular gyrus, right precuneus, left middle frontal gyrus, and right precentral gyrus. MDD patients also showed stronger FC in the left thalamus and reduced FC between the left superior occipital gyrus and left DLPFC seed region. Interestingly, increased FC was related to disease severity (with the right precentral gyrus) and social cognitive dysfunction (with the right angular gyrus) in MDD patients., Limitations: The sample size was relatively small and it is unclear how age may influence FC changes in patients with depression., Conclusions: These findings support changes in FC of the DLPFC in early MDD patients related to cognitive function. FC is a potential biomarker for the diagnosis of MDD., (Copyright © 2022 Elsevier B.V. All rights reserved.)