Traditional frequency domain analysis of heart period (HP) variability allows the estimation of the parasympathetic modulation directed to the heart but the sympathetic one remains largely unknown. Recently, sympathetic and parasympathetic activity indexes (SAI and PAI) have been proposed to address this issue. SAI and PAI were derived from HP variability via the application of an orthonormal Laguerre expansion allowing the separation of HP variations driven by sympathetic and parasympathetic outflows. In this study, SAI and PAI were validated against tonic and variability measures of muscle sympathetic nerve activity (MSNA) and more traditional markers derived from HP variability. Indexes were calculated in 12 healthy subjects (9 females, age from 20 to 36 years, median 22.5 years) undergoing incremental head-up tilt. Results showed that traditional HP and MSNA variability markers as well as SAI and PAI were modified in proportion to the magnitude of the postural challenge. However, SAI was not correlated with any MSNA markers and PAI was not linked to respiratory sinus arrhythmia. SAI and PAI can capture modifications of cardiac control induced by the orthostatic challenge but they might be weak surrogates of vagal and sympathetic activities and/or modulations.Clinical Relevance- SAI and PAI markers are useful to characterize cardiac control but poorly linked with autonomic nervous system state.