A negative outcome can have motivational and emotional consequences on its own (absolute loss) or in comparison to alternative, better, outcomes (relative loss). The consequences of incurring a loss are moderated by personality factors such as neuroticism and introversion. However, the neuronal basis of this moderation is unknown. Here we investigated the neuronal basis of loss processing and personality with functional magnetic resonance imaging in a choice task. We separated absolute and relative financial loss by sequentially revealing the chosen and unchosen outcomes. With increasing neuroticism, activity in the left lateral orbitofrontal cortex (OFC) preferentially reflected relative rather than absolute losses. Conversely, with increasing introversion, activity in the right lateral OFC preferentially reflected absolute rather than relative losses. These results suggest that personality affects loss-related processing through the lateral OFC, and propose a dissociation of personality dimension and loss type on the neuronal level.