Inhibitor of apoptosis proteins (IAPs), including x-linked (XIAP) and cellular IAP 1/2 (cIAP1/2), are important regulators of TNF receptor induced cell death and cytokine production. We have previously demonstrated that, in vitro, IAP loss sensitises macrophages to TNF induced caspase-8 activation and apoptosis, and limits RIPK3 mediated TNF and IL-1β secretion. Here we report that mice with genetic deletion of XIAP and cIAP2 ubiquitously and cIAP1 in myeloid cells (c1^LysMcrex^-/- c2^-/-) develop a mild spontaneous inflammatory arthritis and dermal inflammation, which is associated with increased myelopoiesis and elevated cytokines, particularly IL-1β. In contrast, mice doubly deficient in cIAPs (c1^LysMcrec2^-/-) but retaining XIAP, exhibit severe arthritis accompanied by elevated TNF levels. Predisposition to inflammation upon IAP deletion in myeloid cells was further highlighted by increased disease severity in IL-1β dependent K/BxN serum induced arthritis. Consistent with the role of IAPs as important negative regulators of RIPK3 and caspase-8 activity, we further show that K/BxN arthritis is reduced in mice lacking RIPK3 alone, or in combination with apoptotic caspase-8. In contrast, deficiency in the necroptotic effector MLKL did not alter disease pathogenesis. These results show that deletion of cIAP1 concurrently with either cIAP2 or XIAP is sufficient to cause spontaneous inflammation, albeit with distinct cytokine profiles. Furthermore, our findings overturn the common assumption that reduced inflammatory disease in RIPK3-deficient mice is due to a block in necroptosis.