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Depression symptom severity and cardiorespiratory fitness (CRF) are both predictors of mortality and disability in healthy individuals and patients with heart disease. However, the relationship between the two is unclear. We conducted two systematic reviews and meta-analyses in otherwise healthy individuals and patients with heart disease, respectively, in order to assess the relationship between depression symptom severity and CRF. The first study (Papasavvas et al., 2016b) included 16 studies (4039 participants) and revealed a negative correlation between depression symptom severity and CRF [correlation coefficient (CC -0.16, 95 % CI -0.21 to -0.10)] that appeared stronger in male (CC - 0.22, 95 % CI -0.26 to -0.18) than in female individuals (CC -0.12, 95 % CI -0.19 to -0.05; p = 0.01). The second study (Papasavvas et al., 2017) included 59 studies (25733 participants) and also revealed a negative correlation between depression symptom severity and CRF (CC − 0.15; 95% CI, − 0.17 to − 0.12) that was independent to sex. Within-study level moderator analysis was not possible because raw data were not available for every study. I also assessed the effects of potential moderators of the correlation between depression symptom severity and CRF in 1489 patients with heart disease using linear and logistic regression analysis. Sex (p = 0.007) and BMI (p < 0.001) moderated the correlation: Lower BMI enhanced the correlation, while higher BMI attenuated the correlation in male patients and rendered it statistically not significant in female patients (Papasavvas 2018 - unpublished). We also translated the Cardiac Depression Scale to Arabic and validated it in a representative sample of 260 Arab patients with heart disease (Papasavvas et al., 2016a), in order to assess depression symptom severity in the following study. The subsequent quasi-experimental study aimed to assess whether depression reduces CRF in patients with heart disease but this was eventually not feasible. The above findings have clinical and prognostic implications and should stimulate further research on the effects of improving depression symptom severity on CRF and vice versa. Potential causative relationships between depression symptom severity and CRF should also be investigated.