Behavioral markers of laterality reflecting underlying neurobiological asymmetries between the cerebral hemispheres are related to differential susceptibility to mood disorders. In the present study, we investigated the strength and consistency of a novel behavioral lateralization, head-turning asymmetry, and its relation to behavioral despair in adult female Wistar rats. Head-turning biases were determined in a test where water-deprived rats had to turn their head to right or left to gain access to a water dispenser. This procedure was administered 4 times over 8 days. Four days after the head-turning test, rats were subjected to two forced swim tests separated by 24 h to examine the relationship between head-turning asymmetry and behavioral despair. Rats were administered one more head-turning test session after the second swim test to determine whether behavioral despair induction altered head-turning direction preferences. Results revealed significant correlations among head-turning test sessions indicating head-turning direction preference as measured with our method is a consistent behavioral lateralization. Although most rats were strongly lateralized, there was no bias in either direction at the population level. Importantly, we found that while rats with a left head-turning bias showed a significant increase in the duration of immobility from the first to the second swim test, right-biased rats performed similarly in the two swim tests. Behavioral despair induction did not change head-turning direction preferences. The present findings show that head-turning asymmetries are predictive of mood disorders in rats and may serve as the basis to elucidate the mechanisms relating hemispheric asymmetries to depression in humans.