Investigate the feasibility of a nurse-led mobility protocol and compare the effects of once- versus twice-daily episodes of early therapeutic mobility (ETM) and low- versus moderate-intensity ETM on serum biomarkers of inflammation and selected outcomes in critically ill adults.Randomized interventional study with repeated measures and blinded assessment of outcomes.Four adult intensive care units (ICUs) in two academic medical centers.Fifty-four patients with > 48 hr of mechanical ventilation (MV).Patients were assigned to once- or twice-daily ETM via sealed envelope randomization at enrollment. Intensity of (in-bed vs. out-of-bed) ETM was administered according to protocolized patient assessment.Interleukins 6, 10, 8, 15, and tumor necrosis factor-α were collected from serum before and after ETM; change scores were used in the analyses. Manual muscle and handgrip strength, delirium onset, duration of MV, and ICU length of stay (LOS) were evaluated as patient outcomes.Hypotheses regarding the inflammatory biomarkers were not supported based on confidence intervals. Twice-daily intervention was associated with reduced ICU LOS. Moderate-intensity (out-of-bed) ETM was associated with greater manual muscle test scores and handgrip strength and reduced occurrence of delirium.Findings from this study suggest that nurses can provide twice-daily mobility interventions that include sitting on the edge of the bed once patients have a stable status without altering a pro-inflammatory serum biomarker profile.