Purpose: To investigate systemic leucocyte activity in subtypes of age-related macular degeneration (AMD) and onset of neovascular AMD. Methods: Patients with early and late AMD and age-matched control individuals were recruited consecutively, and venous blood was sampled for differential leucocyte counts. Patients with neovascular AMD were grouped based on time of blood sampling in relation to diagnosis of neovascular AMD: diagnosis of new neovascular AMD more than 30 days before blood sampling, within 30 days of blood sampling and more than 30 days after blood sampling. Results: Of 347 recruited participants, 330 fulfilled the eligibility criteria (77 age-matched controls, 33 with early AMD, 56 with geographic atrophy and 164 with neovascular AMD). We did not find any differences in the differential counts between patients at different stages of AMD and age-matched control individuals. However, lymphocyte and monocytes–basophils–eosinophils mixed (MXD) counts were both significantly increased in patients with new neovascular AMD. Among these patients; higher MXD correlated with lower BCVA, larger central foveal thickness and larger total lesion size; higher lymphocytes correlated with smaller total lesion size; higher neutrophils correlated with CNV lesion size; and higher neutrophil-to-lymphocyte ratio correlated with larger lesion size. Conclusions: Systemic leucocyte activity is associated with onset of CNV in patients with AMD and correlate with lesion size and BCVA, which suggest that acute systemic immune activity may play a role in neovascular flaring of AMD.