Fish mortality in the middle reaches of the Pilcomayo River (Bolivia), locally called ‘borrachera’, can be observed almost every year at the onset of the rainy season. In order to study the potential causes of the ‘borrachera’, suspended sediment (SS) and selected water quality parameters have been monitored from mid‐September until mid‐December 2010. Gill samples were taken and analysed, before and during the ‘borrachera’ event on December 7th 2010. Data on river discharge were obtained from a database. During the sampling period, the river hydrology changed dramatically. At the day of the ‘borrachera’, heavy rains in upstream reaches of the river catchment changed the river from a quiet stream into a turbulent river with extremely high concentrations of SS (> 100 g l−1). This may be caused by the inundation of the entire riverbed, which causes easily erodible material, left on the riverbanks at the end of the former rainy season, to be transported by the river during the first peak discharges. As concentrations of heavy metals in filtered water samples did not show higher values during the ‘borrachera’, it is concluded that the ‘borrachera’ is unlikely to be caused by heavy metal toxicity. Results showed a strong association between the SS concentration and the ‘borrachera’. Gills of fish collected during the ‘borrachera’ were clogged with sediment to such an extent that oxygen uptake became virtually impossible. High SS concentrations are therefore considered to be the cause of this typical fish mortality phenomenon. Copyright © 2012 John Wiley & Sons, Ltd.