Chronic low back pain is one of the most common, costly, and debilitating pain conditions worldwide. Increased mechanistic understanding of the transition from acute to chronic low back and identification of predictive biomarkers could enhance the clinical assessment performed by healthcare providers and enable the development of targeted treatment to prevent and/or better manage chronic low back pain. This study protocol was designed to identify the neurological and transcriptomic biomarkers predictive of chronic low back pain at low back pain onset. This is a prospective descriptive longitudinal inception cohort study that will follow 340 individuals with acute low back pain and 40 healthy controls over 2 years. To analyze the neurophysiological and transcriptomic biomarkers of low back pain, the protocol includes psychological and pain-related survey data that will be collected beginning within 6 weeks of low back pain onset (baseline, 6, 12, 24, 52 weeks, and 2 years) and remotely at five additional time points (8, 10, 16, 20 weeks, and 18 months). Quantitative sensory testing and collection of blood samples for RNA sequencing will occur during the six in-person visits. The study results will describe variations in the neurophysiological and transcriptomic profiles of healthy pain-free controls and individuals with low back pain who either recover to pain-free status or develop chronic low back pain.