This cross-sectional questionnaire study investigated the role of pain (pain severity, radiating pain), work characteristics (physical workload, job stressors, job satisfaction), negative affect and pain-related fear in accounting for low back pain (LBP) and sick leave (SL) in 1294 employees from 10 companies in Belgium and the Netherlands. An increased risk for short-term LBP (1-30 days during the last year) was observed for workers reporting high physical workload (OR=2.39), high task exertion (OR=1.63) and high negative affect (OR=1.03). For prolonged LBP (>30 days during the last year) severe pain (OR=13.03), radiating pain (OR=2.37) and fear of work-related activities (OR=3.17) were significant risk factors. A lack of decision latitude decreased the risk of long-term LBP (OR=0.39). Short-term SL (1-30 days during the last year) was associated with severe pain (OR=2.83), high physical workload (OR=2.99) and high fear of movement/(re)injury (OR=1.88). A lack of decision latitude increased the risk of short-term SL (OR=1.92). Long-term SL (>30 days during the last year) was associated with radiating pain (OR=3.80) and high fear of movement/(re)injury (OR=6.35). A lack of co-worker support reduced the risk of long-term SL (OR=0.27). These results suggest that physical load factors are relatively more important in the process leading to short-term LBP and short-term SL, whereas job stressors, severe pain, radiation, and pain-related fear are more important in determining the further course and maintenance of the inability to work. The potential implications of these findings for primary and secondary prevention, and occupational rehabilitation are discussed.