Our group has previously shown that oxidized phospholipids (OxPL) induce a unique macrophage (MΦ) phenotype known as “Mox,” distinct from pro- and anti-inflammatory M1 and M2 phenotypes. We have also shown that Mox make up 30% of the MΦs found in atherosclerotic lesions. OxPL induce TLR2-dependent inflammatory gene expression in MΦs. TLR2 activation by peptidoglycan was shown to induce accumulation of ceramides, which can alter bioenergetics by inhibiting the mitochondria. Recently, it has been shown that spleen tyrosine kinase (Syk) is phosphorylated upon TLR2 agonist Pam3CSK stimulation in MΦs. The effect of OxPL on bioenergetics has never before been studied. Here we test the hypothesis that OxPL change MΦ bioenergetics and inflammatory capacity via a TLR2-Syk-Ceramide pathway. Using flow cytometry, we found that in mice fed a high-fat diet, more than 20% of all adipose tissue MΦs can be described as Mox. Concomitantly, using immunohistochemistry and liquid-chromatography mass spectrometry, we measured increased levels of OxPL in the stromal vascular fraction of obese murine adipose tissue, as compared to lean controls. We treated bone marrow-derived MΦs (BMDMs) from WT, TLR2-KO, and Syk-KO mice with OxPL and measured bioenergetics using a Seahorse Flux Analyzer. Our results show that OxPL decrease oxygen consumption rate (OCR), a measure of oxidative phosphorylation, and decrease extracellular acidification rate (ECAR), a measure of glycolytic capacity. These MΦs can be described as quiescent, but they still engage in low-level cytokine production. Moreover, OxPL result in the accumulation of ceramides, as quantified by mass spectrometry. Finally, using Syk-KO MΦs and Syk inhibitors, we show that OxPL-induced inflammatory gene expression and ceramide accumulation are dependent on Syk. In summary, our results demonstrate that OxPL accumulate in obese adipose tissue and induce a change in the inflammatory and metabolic profiles of MΦs, involving a TLR2-ceramide-Syk dependent pathway. These results suggest that OxPL are triggers of adipose tissue inflammation and subsequent development of insulin resistance. Furthermore, we identify Syk as a therapeutic target for inhibiting diet-induced adipose tissue inflammation and insulin resistance.