The quality of day-old chick placement and management upon arrival have a major impact on first-week mortality (FWM) and subsequent welfare in layers. The present study investigated FWM and causes of FWM in 50 flocks of layers. Post mortem results from 983 chickens showed that 50% died from infections, whereas noninfectious causes, in particular dehydration and nephropathy with visceral gout, made up the remaining causes of mortality. Escherichia coli and Enterococcus faecalis were identified as the most significant bacterial pathogens associated with FWM. Statistical analysis demonstrated a significant correlation between FWM and total mortality during rearing, and a model predicting total mortality in the rearing period based on FWM was established. A statistically significant correlation between FWM and uniformity of the flock was not demonstrated at 1–2 wk of age or at approximately 15 wk of age. Genetic characterization of E. coli and E. faecalis provided evidence for a polyclonal nature of these infections in affected flocks, indicating different sources of infection. Results obtained underline the importance of minimizing FWM to a level less than 1%.