Although there has been much interest in understanding the effect of gratitude on health-related outcomes, this remains an understudied area of research, particularly regarding mechanisms and measurement of biological outcomes. The present study explored whether a gratitude intervention could reduce inflammatory outcomes and whether this occurred through increased support-giving. Healthy women (n = 76) were randomly assigned to a 6-week gratitude intervention (i.e., writing on topics intended to induce gratitude) or a control condition (i.e., neutral writing). Support-giving and markers of inflammation were measured pre- and postintervention. Those in the gratitude intervention (vs. control) reported higher postintervention levels of support-giving. Moreover, those with lower levels of psychological distress gave more support as a function of the gratitude intervention. Regarding inflammatory outcomes, although there was no effect of the gratitude intervention on postintervention inflammatory markers, increases in support-giving across the entire sample were related to decreases in inflammatory markers. These results, along with a scarcity of work in this area, suggest that further work is needed to more fully understand the relationships between gratitude and biological markers relevant to health. Finally, these novel findings linking support-giving and decreases in inflammation also indicate that the mammalian caregiving system, associated with enhanced support-giving and reduced physiological stress responding, is a mechanism worth further examination to elucidate the links between social support and health. (PsycINFO Database Record (c) 2019 APA, all rights reserved).