Here, we present a study of how liposomes are loaded and release their contents during their electrochemical detection. We loaded 200 nm liposomes with a redox mediator, ferrocyanide, and used amperometry to detect their collision on a carbon-fiber microelectrode (CFE). We found that we could control the favorability of their electroporation process and the amount of ferrocyanide released by modifying the osmolarity of the buffer in which the liposomes were suspended. Interestingly, we observed that the quantity of the released ferrocyanide varied significantly with buffer osmolarity in a nonmonotonic fashion. Using stimulated Raman scattering (SRS), we confirmed that this behavior was partly explained by fluctuations in the intravesicular redox concentration in response to osmotic pressure. To our surprise, the redox concentration obtained from SRS was much greater than that obtained from amperometry, implying that liposomes may release only a fraction of their contents during electroporation. Consistent with this hypothesis, we observed barrages of electrochemical signals that far exceeded the frequency predicted by Poisson statistics, suggesting that single liposomes can collide with the CFE and electroporate multiple times. With this study, we have resolved some outstanding questions surrounding electrochemical detection of liposomes while extending observations from giant unilamellar vesicles to 200 nm liposomes with high temporal resolution and sensitivity.