Although it has been shown that microchip electrophoresis (MCE) with electrochemical detection can be used to separate and detect electroactive species, there is a need to increase the separation performance of these devices so that complex mixtures can be routinely analyzed. Previous work in the MCE has demonstrated that increasing the separation channel length leads to an increase in resolution between closely eluting analytes. This paper details the use of lengthened serpentine microchannels for MCE and electrochemical detection where a palladium decoupler is used to ground the separation voltage so that the working electrodes remain in the fluidic network. In this work, palladium electrodepositions were used to increase the decoupler surface area and more efficiently dissipate hydrogen produced at the decoupler. Dopamine and norepinephrine, which only differ in structure by a hydroxyl group, were used as model analytes. It was found that increasing the separation channel length led to improvements in both the resolution and the number of theoretical plates for these analytes. The use of a bilayer valving device, where PDMS-based valves are utilized for the injection process, along with serpentine microchannels and amperometric detection resulted in a multi-analyte separation and an average of 28 700 theoretical plates. It was also shown that the increased channel length is beneficial when separating and detecting analytes from a high ionic strength matrix. This was demonstrated by monitoring the stimulated release of neurotransmitters from a confluent layer of PC 12 cells.