Background: Information on prognostic factors for duration of sick leave due to low-back pain (LBP) is growing. In this prospective cohort study prognostic factors for duration of sick leave and course of disability were identified in a very early stage of sick leave due to LBP in an occupational health care setting. Methods: A total of 615 workers calling in sick from work due to LBP at an occupational health service (OHS) of one institution completed a questionnaire. Duration of follow-up was 26 weeks. Prognostic factors were identified by means of Cox regression analysis and multiple linear regression analysis, and explained variance was calculated. Results: Median time to first return to work (RTW) was 5 days (Inter Quartile Range (IQR) = 2–12). Median time to lasting return to work (LRTW) was 6 days (IQR = 3–13). The final model for delayed RTW included self-reported expected duration of sick-leave, treatment by GP or specialist, care-seeking, diminished mobility, and the interaction between care-seeking and diminished mobility. The final model for LRTW included: self-reported expected duration of sick-leave, treatment by GP or specialist, care-seeking, the interaction between the self-reported expected duration of sick-leave and seeking care at OHS, complaints due to job stress, diminished mobility, and the interactions between expected duration of more then 10 days and seeking OP care and diminished mobility. Median total days on sick leave (TDSL) was 6 days (IQR = 3–13 days). The final model for TDSL included: age, expected duration of sick leave, treatment by GP or medical specialist, seeking OP care, complaints due to physical load, and diminished mobility. Explained variance (R²) of these models ranged from 30 to 35%. Conclusions: Poor prognosis for duration of sick leave can be identified by means of a simple questionnaire administered on the first day of sick leave. Workers at high risk for longer duration of sick leave (all outcomes) expected to stay off work longer, were already being treated by a MD, sought OP care, and had diminished mobility. In case of delayed LRTW workers reported job stress as a possible cause of sick leave. Interactions were found in both RTW and LRTW between care-seeking and diminished mobility and in LRTW between expected duration of sick leave and seeking OP care. Older age increased TDSL with borderline significance.