The ageing process is a complex phenomenon that impacts the immune system, leading to changes in the pattern of serum soluble mediators. In the present study, the serum levels of several chemokines, pro-inflammatory/regulatory cytokines and growth factors were quantified by high-throughput microbeads array in serum samples from 541 healthy subjects at distinct age ranges (3Yrs to >70Yrs). A broad increase in serum soluble mediators was observed at 6–10Yrs with subsequent decline at 11–20Yrs and 21–30Yrs followed by a second round of upregulation starting at 31–40Yrs, with a large increase at 51–60Yrs and a marked decline at age >70Yrs. Heatmap and signatures of serum soluble mediators demonstrated a bimodal profile with one peak at 6–10Yrs and a second wave around 61–70Yrs. A universal decline was observed later at age >70Yrs. In males, the second wave started earlier at 31–40Yrs with a peak at 51–60Yrs and a further smooth decline towards >70Yrs. Conversely, in females, the first peak extended from 3–5Yrs to 6–10Yrs and the second wave starting around 41–50Yrs with a peak at 61–70Yrs followed by a sharp decline at >70Yrs. Overall, CCL11, CXCL8, IL-1β, IL-6 were underscored as universal age-related biomarkers with higher levels observed at later age ranges (after 31–40Yrs) and TNF with increased levels starting at early age ranges. Data analysis demonstrated that the highest neighborhood connectivity amongst soluble mediators occurred at 3–5Yrs, with distinct declining and strengthening rhythm in males and females. Notably, rebuilding re-arrangements were usually earlier and more frequent in females (at 11–20Yrs, 51–60Yrs and >70Yrs) than in males (at 21–30Yrs, 61–70Yrs). Overall, this study provided a comprehensive landscape of evidence portrayed by distinct waves, rhythms and dynamic network connectivity along healthy ageing with differences in magnitude and timing reported for sexes.