OBJECTIVE: Pathomechanisms of sedentary behavior (SB) are unclear. We conducted a systematic review to investigate the associations between SB and various biomarkers in older adults. METHODS: Electronic databases were searched (MEDLINE, EMBASE, CINAHL, AMED) up to July 2015 to identify studies with objective or subjective measures of SB, sample size≥50, mean age≥60years and accelerometer wear time ≥3 days. Methodological quality was appraised with the CASP tool. The protocol was pre-specified (PROSPERO CRD42015023731). RESULTS: 12701 abstracts were retrieved, 275 full text articles further explored, from which 249 were excluded. In the final sample (26 articles) a total of 63 biomarkers were detected. Most investigated markers were: body mass index (BMI, n=15), waist circumference (WC, n=15), blood pressure (n=11), triglycerides (n=12) and high density lipoprotein (HDL, n=15). Some inflammation markers were identified such as interleukin-6, C-reactive protein or tumor necrosis factor alpha. There was a lack of renal, muscle or bone biomarkers. Randomized controlled trials found a positive correlation for SB with BMI, neck circumference, fat mass, HbA1C, cholesterol and insulin levels, cohort studies additionally for WC, leptin, C-peptide, ApoA1 and Low density lipoprotein and a negative correlation for HDL. CONCLUSION: Most studied biomarkers associated with SB were of cardiovascular or metabolic origin. There is a suggestion of a negative impact of SB on biomarkers but still a paucity of high quality investigations exist. Longitudinal studies with objectively measured SB are needed to further elucidate the pathophysiological pathways and possible associations of unexplored biomarkers.