The recognition of carbohydrate moieties by cells of the innate immune system is emerging as an essential element in anti-fungal immunity, but few carbohydrate receptors have been characterised, despite the number and diversity of lectins expressed by innate immune cells. We demonstrate a novel role for the c-type lectin Mincle in macrophage responses to C. albicans. Mincle was observed to localise in the phagocytic cup of macrophages in response to a range of stimuli. Loss of Mincle reduced macrophage TNF production both in vivo and in vitro, but did not alter the number of Candida yeast phagocytised. Mice lacking Mincle showed a significantly increased susceptibility to systemic candidiasis. Thus Mincle contributes a novel and non-redundant role in the induction of inflammatory signalling in response to C. albicans infection.