Metastatic melanoma is the third most common cancer in Australia. >40% of melanoma patients harbour a V600E mutation, which causes the overt activation of the BRAF kinase and downstream mitogen-activated protein kinase (MAPK) pathway, resulting in uncontrolled melanocyte proliferation. Inhibitors targeting BRAF (Dabrafenib) and other members of the MAPK/ERK (MEK) pathway (Trametinib) have been used clinically to curb this proliferation with much success. However, tumour resistance to single inhibitor therapies have emerged, prompting the preliminary use of combination therapies with other MEK inhibitors as well as with checkpoint inhibitors. Moreover, the impacts of off-target effects on the immune system and specifically on dendritic cells (DCs) are not well-characterised. Therefore, we sought to investigate how DCs might respond to Dabrafenib and Trametinib treatment. With the use of Flt3L-derived bone marrow DCs (FLDCs), we discovered that Dabrafenib, but not Trametinib, treatment increased surface activation marker expression on all DC subsets. We also found that Dabrafenib treatment enhanced pro-inflammatory cytokine (IL-6, IL-1b), chemokine (CXCL1, RANTES, MIP-1b) and IFN-Lambda production by sorted DC subsets stimulated with TLR3/7/9 agonists. Intriguingly, we have also observed that Dabrafenib paradoxically induced ERK phosphorylation in FLDCs, which was enhanced upon TLR3 stimulation. Thus, the use of Dabrafenib to treat melanoma patients could inadvertently affect DC function and we hope that by understanding the mechanisms behind these inhibitor treatments, we can specifically target them to improve treatment outcomes and combat resistance.