This study aimed to examine the longitudinal effects of a short-term mindfulness intervention on psychological and immune variables in a student sample with moderate depressive symptoms. 64 college females were assigned to a mindfulness intervention group or a contact-control condition. Participants received three separate assessments: (a) before treatment initiation (baseline), (b) following treatment completion (6-week follow-up), and (c) 3-months after treatment completion (3-month follow-up). At each time point, self-report data and salivary samples of interleukin-6 and TNF-alpha were collected. Preliminary data suggests that no significant differences in self-reported outcomes emerged pre-post intervention when comparing treatment conditions (MBSR vs. contact-control). Instead, both groups demonstrated reductions in psychological symptoms and improvements in well-being over time. Examination of salivary cytokines revealed that IL-6 decreased more in the MBSR condition than in the contact-control condition. There was a similar condition difference in change over time for TNF-α; however, the effect was only marginally significant. Supplemental within-group analyses for the MBSR condition indicated that changes in IL-6 were maintained to a large degree. Identical analyses carried out for TNF-α suggested that TNF-α actually decreased significantly from baseline to the 6-week follow-up, but there was only a marginally significant trend toward maintenance of such decreases.