Magnetic resonance imaging (MRI) studies have consistently identified a high incidence of silent brain infarction (SBI) after cardiac intervention. The frequent occurrence, objective measurement and clinical sequelae of SBI have seen interest in their detection for both research and clinical purposes. However, MRI is expensive, time-consuming, unsafe in acutely-ill patients, and not always available, limiting its use as a routine screening tool. For this purpose, a blood biomarker of SBI would be the "Holy Grail." By performing targeted profiling of serologic biomarkers this study aimed to assess their potential as screening tools for perioperative SBI. This is a nested case-control study of 20 prospectively recruited patients undergoing transcatheter aortic valve implantation under general anesthesia. Clinical and diffusion-weighted MRI assessments were performed at baseline and on day 3 postprocedure to identify the presence (cases) or absence (controls) of new SBI. Blood was collected at baseline and 24, 48, and 72 hours postprocedure and analyzed for S100 calcium-binding protein B, neuron specific enolase (NSE), matrix metalloproteinase 9 (MMP 9), and glial fibrillary acidic protein. Best-fit polynomial curves using a smoothing model were generated for each biomarker and inferential testing at a predefined 24-hour postprocedure timepoint detected a significant difference for MMP 9 (72,435; SEM: 25,030; p = 0.027). Longitudinal regression revealed a statistically significant case-control difference for both NSE (mean: 10,747; SEM: 3,114) and MMP 9 (63,842; SEM: 16,173). In conclusion, NSE and MMP 9 are present in higher levels following SBI and warrant further investigation for their utility as screening tools.