During pregnancy, the developing foetus must be protected from the maternal immune system. The maternal immune system is considered to be in an altered or compromised state during pregnancy and this is achieved by factors released by the placenta, including hormones and cytokines. Placental malaria is characterised by the accumulation of Plasmodium falciparum-infected erythrocytes (IE) in the placenta, and results in poor outcomes for both the mother and the foetus, including anaemia, low birth weight and miscarriage. Pregnancy-specific IE bind to the glycosaminoglycan chondroitin sulphate A within the placenta. We hypothesise that chondroitin sulphate containing proteoglycans act as immune system modulators during pregnancy and that the binding of IE to chondroitin sulphate A in the placenta allows the establishment of the initial parasite niche. Here, we show that bovine-derived chondroitin sulphate A dampens the immune response of human peripheral blood mononuclear cells (PBMCs) to IE and bacterial products. In the presence of chondroitin sulphate A, monocytes produced less tumour necrosis factor, had differential expression of pattern recognition receptors and were skewed towards a classical phenotype. Finally, we show that proteoglycans derived from human placental tissue also modulate the monocyte response to pathogen products.