This report is a secondary analysis of data from a larger study of a nurse-led early therapeutic mobility intervention among patients receiving mechanical ventilation. This analysis evaluated whether intervention frequency or intensity was associated with pain or fatigue. Frequency was defined as once-daily versus twice-daily interventions. Intensity was defined as low (in-bed activities) or moderate (out-of-bed activities). Thirty-nine patients self-reported pain and fatigue immediately before and after the intervention. Neither pain nor fatigue increased significantly (mean increase, <1 [scale of 0-10] for 95% of inter-ventions). Four patients reported decrements in pain; 1 reported a decrease in fatigue. Less than 5% of enrolled patients indicated a score change of +4 to +6 for pain or fatigue, typically with the first intervention that included sitting at the edge of the bed. Future research could examine the distress associated with these symptoms in critically ill adults receiving early therapeutic mobility interventions.