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Abstract Background One critical premise of disease‐related biomarkers is the definition of the counterpart normality. Contrary to pre‐clinical models that can be carefully tailored according to scientific need, heterogeneity and uncontrollability is the essence of humans in health studies. Fully characterization of consistent parameters that define the normal population is the basis to individual differences normalization irrelevant to a given disease process. Self claimed normal status may not represent health because asymptomatic subjects may carry chronic diseases or diseases at their early stage such as cancer, diabetes and hypertension. Methods This paper exemplifies the characterization of the suboptimal health status (SHS) which represents a new public health problem in a population with ambiguous health complaints such as general weakness, unexplained medical syndrome and chronic fatigue. We applied clinical informatics approaches and developed a questionnaire for measuring SHS. The validity and reliability of this approach were evaluated in a small pilot study and then in a cross‐sectional study of 3,405 individuals. Results The final questionnaire congregated into a score (SHSQ‐25) which could significantly distinguish among several abnormal conditions. Conclusion SHSQ‐25 could be used as a translational medicine instrument for health measuring in the general population.