This study tested the hypothesis: "does adaptation to fluctuating salinities lead to enhanced survival of the harpacticoid copepod M. parva when exposed to a combination of particle associated chlorpyrifos (CPF) exposure and hypoosmotic stress during a 96h sediment toxicity test?" The CPF exposure concentrations of 5.89-5.38mug/kg and the salinity decrease from 15 to 3ppt were based on conditions observed in the temporarily open Lourens River estuary, South Africa, in order to simulate changes during a runoff event. Results of the three-factorial ANOVA showed that pre-adaptation to varying salinities (p=0.02; p=0.001), salinity decrease (p=0.035; p<0.001), and CPF exposure (p<0.001; p<0.001), all had a significant negative impact on the survival rate of female and male M. parva, with a higher sensitivity of males specimens. The significant two-way interaction of salinityxadaptation for females and males (p=0.021; p<0.001), indicate that adaptation to fluctuating salinities was beneficial for male and female copepods, but the hypothesis of a three-way interaction was not supported. However, a trend indicated a lower survival rate of non-adapted females and males exposed to CPF and hypoosomotic stress (38+/-17%; 0+/-0%), compared to pre-adapted organisms (59+/-6.6%; 8.9+/-10%), which requires further elucidation. This study has important implications for the management of temporarily open estuaries in South Africa regarding regulation of freshwater abstraction from rivers.