The negative binomial distribition parametrized by mean and size can be given by $$ \DeclareMathOperator{\P}{\mathbb{P}} \P (X=k) = \binom{k+m-1}{k}\left( \frac{m}{m+\mu} \right)^m \left( \frac{\mu}{m+\mu} \right)^k $$ for the outcome $k$ a nonnegative integer, and $\mu>0$ the mean, $m>0$ the size. I will do the calculations by maple. The Fisher information matrix (of size $2\times 2$) has components $I_{\mu\mu}, I_{\mu m} \text{ and } I_{\mu m}$ given by $$ \DeclareMathOperator{\E}{\mathbb{E}} I_{ij}=-\E\left\{ \frac{\partial^2}{\partial \theta_i \partial\theta_j}\log f(X;\theta)|\theta \right\} $$ where here $\theta=(\mu, m)$. Then we (maple code at the end of post) find $$ I_{\mu\mu}=\frac{m}{(m+\mu)\mu} $$ The diagonal term is simplest, it reduces to zero! That is the beauty of the mean parametrization $$ I_{\mu m}=0 $$ For the last term, I cannot find a simple closed form. The result will involve a digamma function written $\Psi$ (log derivative of gamma function) and result will be a somewhat complex infinite series, which must be evaluated numerically: $$ I_{mm}=\sum_{k=0}^\infty \binom{k+m-1}{k}\left\{ -m^{m-1}\mu^k (m+\mu)^{-m-2-k} \left( m(m+\mu)^2 \Psi(k+m) -m(m+\mu)^2 \Psi(m) +mk+\mu^2 \right) \right\} $$ or maybe some other form could be found (later, the NIST handbook of mathematical functions has some nice integral formulas for $\Psi$ which could be useful). But, maybe numerical integration is not so much better than numerical summation? Below some maple code (and output): f := binomial(k+m-1,k)*(m/(m+mu))^m * (mu/(m+mu))^k m k / m \ / mu \ f := binomial(k + m - 1, k) |------| |------| \m + mu/ \m + mu/ lf := ln( binomial(k+m-1,k) ) + m*ln( m/(m+mu) ) + k* ln( mu/(m+mu) ) assuming m>0,mu>0; / m \ / mu \ lf := ln(binomial(k + m - 1, k)) + m ln|------| + k ln|------| \m + mu/ \m + mu/ simplify( -sum(f*diff(lf,mu,mu),k=0..infinity ) ) assuming m>0,mu>0; m ----------- (m + mu) mu simplify( -sum(f*diff(lf,mu,m),k=0..infinity ) ) assuming m>0,mu>0; 0 simplify( -sum(f*diff(lf,m,m),k=0..infinity ) ) assuming m>0,mu>0; infinity ----- \ ) (m - 1) (-m - 2 - k) k - / m (m + mu) mu binomial(k + m - 1, k) ----- k = 0 / 2 2 2\ \m (m + mu) Psi(1, k + m) - m (m + mu) Psi(1, m) + m k + mu /