AbstractPlasticized PVC membrane‐based potassium or sodium ion‐selective optodes were incorporated into sampling capillaries in combination with sol‐gel‐based hydrogen ion‐selective optodes for the sampling and analysis of minute tear fluid samples. The performance characteristic of the K+/pH and Na+/pH sensor arrays were optimized for an adequate dynamic response range, sensitivity, stability, and response time. The precision and accuracy of the combined sampling/measurement system was evaluated both in stopped flow and continuous flow modes using aqueous standard solutions. By using a two point calibration protocol, with pH standards bracketing the sample, the pH of 20 µL pooled human tear samples could be determined with a precision less than ±0.03 pH units. Errors in the pH measurements have a significant influence on the attainable precision and accuracy of the ion‐exchange‐based K+ and Na+ optodes. Nevertheless, the results of the quantitative assessment of the K+ and Na+ concentrations in “check” standards and pooled human tear fluid samples were within ±5 % of the nominal values or of the results of the determinations with atomic absorption spectrophotometry. Cationic surfactants in artificial tear drops were found to interfere with the K+ and Na+ optode responses. No interference was detected in the presence of anionic and nonionic surfactants.