Ensemble square root filters can either assimilate all observations that are available at a given time at once, or assimilate the observations in batches or one at a time. For large-scale models, the filters are typically applied with a localized analysis step. This study demonstrates that the interaction of serial observation processing and localization can destabilize the analysis process and examines under which conditions the instability becomes significant. The instability results from a repeated inconsistent update of the state error covariance matrix that is caused by the localization. The inconsistency is present in all ensemble Kalman filters, except the classical ensemble Kalman filter with perturbed observations. With serial observation processing, its effect is small in cases when the assimilation changes the ensemble of model states only slightly. However, when the assimilation has a strong effect on the state estimates, the interaction of localization and serial observation processing can significantly deteriorate the filter performance. In realistic large-scale applications, when the assimilation changes the states only slightly and when the distribution of the observations is irregular and changing over time, the instability is likely not significant.