Aim: Despite curative surgery, 25% of patients with Stage II colorectal cancer will relapse due to minimal residual disease (MRD). Markers of immune function, such as the neutrophil to lymphocyte ratio (NLR), may be associated with MRD defined by bone marrow micro-metastasis (mM) and circulating tumour cells (CTCs). Method: A prospective cohort study of consecutive patients with Stage II colon cancer patients attended at a single centre between 2007 and 2014. Blood and bone marrow samples were taken to detect CTCs and mM using immunocytochemistry with anticarcinoembryonic antigen 1 month after surgery. The NLR and absolute neutrophil and lymphocyte counts were determined immediately pre-surgery and 1 month post-surgery. These were compared with the sub-types of MRD: group I MRD(−); group II mM positive and group III CTC positive. Cut-off values of the NLR of >3.0 and >5.0 were used. Follow-up was for up to 5 years or relapse and disease-free survival (DFS) was calculated using Kaplan-Meier analysis. Results: In all, 181 patients (99 women) participated. Mean age was 68 years. Median follow-up was 4.04 years: I, N = 105; II, N = 36; III, N = 40. The NLR significantly decreased post-surgery only in group I patients. The frequency of NLR >3.0 and >5.0 was significantly higher in group III; between groups I and II there was no significant difference.5-year DFS was 98% in group I, 68% in group II and 7% in group III.Conclusions: Patients with a significantly higher immune dysfunction had a shorter time to disease progression, a worse DFS and the presence of CTCs.