Major depressive disorder (MDD) is a debilitating and prevalent disorder associated with lower quality of life and substantial economic burden. Recently, there has been strong interest in respiratory sinus arrhythmia (RSA) as a biological predictor of later depression. Theoretical work suggests that higher resting RSA indexes physiological flexibility and better emotion regulation whereas lower RSA may mark vulnerability for psychopathology. However, empirical findings have varied. This study examined whether lower resting RSA predicted later depressive symptoms in a sample of healthy young adults across one year (n = 185). Results indicate that year one (Y1) resting RSA predicted Y2 depressive symptoms. This finding remained significant when accounting for the stability of RSA and depressive symptoms across both time points and when including trait anxiety, body mass index, and medication use in statistical models. Findings provide further support for RSA as a promising biological marker for understanding and predicting depressive symptoms.