Pain and fatigue are early indicators of musculoskeletal strain. This study examined associations among eight physical demands and inadequate sleep, pain medication use, and absenteeism in 3727 working registered nurses (RNs). Among the demands, awkward head/arm postures were associated with each outcome (inadequate sleep: odds ratio [OR], 1.96; 95% confidence interval [CI], 1.41 to 2.72; pain medication: OR, 1.65; CI, 1.12 to 2.24; absenteeism: OR, 1.60; CI, 1.26 to 2.04). A dose-response relationship was present; as the number of demands increased, the likelihood of each outcome increased. Odds ratios for eight demands versus no demands were as follows: inadequate sleep (OR, 5.88; CI, 2.30 to 15.50), pain medication (OR, 3.30; CI, 1.34 to 8.11), and absenteeism (OR, 2.13; CI, 1.15 to 3.94). Adjustment using multiple logistic regression for lifestyle, demographics, and work schedule did little to alter the findings. Interventions to promote nurses’ health should limit the physical demands of the work.