Owing to the COVID-19 pandemic, organizations worldwide have implemented remote working arrangements that have blurred the work–family boundaries and brought to the forefront employees’ sense of disconnectedness from their workplace (i.e., organizational disconnectedness) as a concern for multiple organizational outcomes. Cynicism, a job burnout subdimension, refers to a negative and excessively detached response to relational overload at work. While both workplace disconnectedness and cynicism involve a toxic sense of detachment, they refer to different psychological mechanisms. The present study aims to examine how employee workplace disconnectedness differs from their cynicism, and how both constructs differentially exert their detrimental effects on employee performance, work–family interface, and wellbeing. Using anonymous survey data collected online in 2021 and 2022 from a sample of in-person and flexible workers nested within organizations, conceptual distinctiveness between workplace disconnectedness and cynicism was supported. Measurement invariance across the two groups was supported, and subsequent structural invariance analyses suggested a similar pattern of results for flexible and in-person workers. Specifically, compared to disconnectedness, cynicism exerted higher negative effects on mental health and higher positive effects on cognitive failures and family-to-work conflict. Conversely, compared to cynicism, disconnectedness exerted higher negative effects on performance and work-to-family conflict. That is, feeling indifferent toward others particularly affects mental health and errors, while feeling excluded especially hampers productivity and family life. Theoretical and practical (e.g., inclusive leadership, support groups) implications of these results are discussed in light of the globally rising rates of hybrid work arrangements and related costs for employee wellbeing and productivity.