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Objectives Antiphospholipid syndrome (APS), a rare autoimmune disease, is the leading cause of strokes in patients under 50, and APS antibodies are estimated to be involved in 15% of all miscarriages. Although APS can present independently it can co-exist with other autoimmune disorders, most commonly Systemic Lupus Erythematosus(SLE). Whilst isolated-APS and isolated-SLE are well studied, less is known of the additive effect of co-existence of both disorders(APS/SLE) on a cellular and molecular level. Monocytes play a key role in both APS and SLE, with their activation linked to disease pathogenesis. This study aimed to assess the role of monocytes in APS/SLE and unravel the additive effects of APS and SLE on monocyte function.Methods Isolated peripheral blood mononuclear cells (PBMCs) from donors were analysed in a 34-colour spectral flow cytometry panel to assess monocyte phenotype/function in patients with APS, SLE and APS/SLE compared to healthy controls (HCs)(n=6 per group).Results High-dimensional analyses identified the classical (CM;CD14+CD16-), intermediate (IM;CD14+CD16+) and non-classical (NCM;CD14loCD16+) monocyte subsets. There were no differences in the frequencies of total monocytes nor monocyte subsets between HCs and patient groups with CMs accounting for ~60-90% of total monocytes across conditions. Analyses of these CMs revealed a strong signature for intracellular complement production in APS/SLE that is lower in isolated-APS and SLE. We found that the frequency of C1q+C3+ monocytes was elevated across patient groups but was significantly increased in APS/SLE. This expansion coincided with a contraction in double-negative (C1q-C3-) monocytes which were found at the highest frequency in HCs. Further analyses of these C1q+C3+ monocytes revealed that they are significantly enriched for markers associated with both coagulation (Tissue Factor) and complement activation (C5-C9). Additionally, these monocytes had significantly higher expression of pro-inflammatory cytokines (TNFα, IL-1β) and type I interferons (IFNα/β).Conclusions This study highlights the additive effects of complement/coagulation dysfunction seen in SLE and APS in patients with a diagnosis of both autoimmune conditions. We have identified a novel monocyte subset with increased intracellular complement expression capable of producing coagulation factors as well as pro-inflammatory cytokines. This subset is uniquely expanded in APS/SLE and represents an attractive future therapeutic target for disease management.