Environmental variables (including natural and anthropogenic stressors) and meiobenthic communities were sampled in a ‘natural’ (Rooiels) and a ‘disturbed’ (Lourens) estuary in the Western Cape, South Africa, bimonthly for 20 months. A primary aim of the study was to assess if the meiobenthic community structure is driven by different variables when comparing ‘natural’ versus ‘disturbed’ system. Due to the much smaller catchment of the Rooiels Estuary, many environmental variables were significantly different (p< 0.001) from the variables in the Lourens Estuary, e.g. salinity, temperature, pH, total suspended solids, nitrate and depth. No pesticide concentrations were expected in the Rooiels Estuary due to the absence of agricultural development in the catchment. However, chlorpyrifos (8.9 μg/kg), prothiofos (22.0 μg/kg) and cypermethrin concentrations (0.42 μg/kg) were detected frequently, with the highest concentrations recorded during the summer months. Principal response curve analysis showed that temporal variability between sampling dates explained 42% of the variance in environmental variables and pesticide concentrations and spatial variability between the 2 estuaries explained 58%. Variables contributing most to the differences were higher concentrations of endosulfan, p,p-DDE and nitrate concentrations in the Lourens Estuary and larger grain size and higher salinity at the bottom in the Rooiels Estuary. In general the meiofaunal community in the Rooiels Estuary showed a significantly higher number of taxa (p< 0.001), a significantly higher Shannon Wiener Diversity Index (p<0.001) and a generally lower meiofaunal abundance with less variability than in the Lourens Estuary. The differences were mostly explained by a higher abundance of Cypretta and Darcythompsonia in the Rooiels Estuary and a higher abundance of Thermocyclops and Canthocamptus in the Lourens Estuary. The variables explaining a significant part (14%) of the variance in meiofaunal abundance in the Rooiels Estuary were salinity and temperature, with the Redundancy Analysis indicating that the abundance of most of the taxa increased with higher salinity and temperature, e.g. Upogebia, Nereis, Uroma and nematodes were clearly positively correlated to salinity and temperature. The variables explaining a significant part of the variance in the dataset (43%) within the Lourens Estuary were also salinity and temperature but included chlorpyrifos, nitrate and flow (including river and tidal flow).