The goal of this study was to describe the quality of naturalistic communication between patients with advanced cancer and their spouse caregivers using observational methods. We also assessed the association between patient and caregiver communication behaviors and psychological and physical health using the actor-partner interdependence model. Data on 81 dyads were gathered as part of a prospective observational study. Patients with advanced cancer and their spouse caregivers completed demographic, physical health, and emotional well-being questionnaires. Cancer and relationship communication captured in "day-in-the-life" audio recordings were coded using Gottman's Turning System to assess the quality of bids for attention and responses. Bids for attention were most often informational (Low Bids) and responses were mostly positive and effortful (Turn Towards); patients and caregivers did not significantly differ in communication behavior. More effortful bids for attention (High Bids) were associated with more positive and effortful responses. Patient communication behaviors were significantly associated with caregiver emotional well-being, whereas caregiver communication behaviors were significantly associated with their own emotional well-being and patient physical health. While patients may benefit from caregivers' more positive and engaged communication at home, the emotional labor of focusing on and engaging the patient may take a toll on caregivers' own well-being. This work contributes to the understanding of what everyday communication looks like for patients with advanced cancer and their spouse caregivers and how this communication may impact physical and psychological health. Our findings provide a foundation to develop guidelines for psychosocial couple-based interventions.