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 at a very early stage of sick leave due to LBP. 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. 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). Analysis resulted in final models for delayed RTW, for LRTW, and for total days on sick leave (TDSL). Explained variance (R2) of these models ranged from 30 to 35%. On the basis of the models is concluded that 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.